Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective</title><author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name></author><author><name sortKey="Islam, Md Sahidul" sort="Islam, Md Sahidul" uniqKey="Islam M" first="Md Sahidul" last="Islam">Md Sahidul Islam</name></author><author><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name></author><author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name></author><author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32226288</idno><idno type="pmc">7098036</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036</idno><idno type="RBID">PMC:7098036</idno><idno type="doi">10.7150/ijbs.45538</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001795</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001795</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective</title><author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name></author><author><name sortKey="Islam, Md Sahidul" sort="Islam, Md Sahidul" uniqKey="Islam M" first="Md Sahidul" last="Islam">Md Sahidul Islam</name></author><author><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name></author><author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name></author><author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name></author></analytic><series><title level="j">International Journal of Biological Sciences</title><idno type="eISSN">1449-2288</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gralinski, Le" uniqKey="Gralinski L">LE Gralinski</name></author><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burki, Tk" uniqKey="Burki T">TK Burki</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Guan, Wj" uniqKey="Guan W">WJ Guan</name></author><author><name sortKey="Ni, Zy" uniqKey="Ni Z">ZY Ni</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Liang, Wh" uniqKey="Liang W">WH Liang</name></author><author><name sortKey="Ou, Cq" uniqKey="Ou C">CQ Ou</name></author><author><name sortKey="He, Jx" uniqKey="He J">JX He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C Huang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Ren, L" uniqKey="Ren L">L Ren</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Chen, N" uniqKey="Chen N">N Chen</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M Zhou</name></author><author><name sortKey="Dong, X" uniqKey="Dong X">X Dong</name></author><author><name sortKey="Qu, J" uniqKey="Qu J">J Qu</name></author><author><name sortKey="Gong, F" uniqKey="Gong F">F Gong</name></author><author><name sortKey="Han, Y" uniqKey="Han Y">Y Han</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, P" uniqKey="Zhou P">P Zhou</name></author><author><name sortKey="Yang, Xl" uniqKey="Yang X">XL Yang</name></author><author><name sortKey="Wang, Xg" uniqKey="Wang X">XG Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B Hu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, A" uniqKey="Wu A">A Wu</name></author><author><name sortKey="Peng, Y" uniqKey="Peng Y">Y Peng</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B Huang</name></author><author><name sortKey="Ding, X" uniqKey="Ding X">X Ding</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Niu, P" uniqKey="Niu P">P Niu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author><author><name sortKey="Azhar, Ei" uniqKey="Azhar E">EI Azhar</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xie, X" uniqKey="Xie X">X Xie</name></author><author><name sortKey="Zhong, Z" uniqKey="Zhong Z">Z Zhong</name></author><author><name sortKey="Zhao, W" uniqKey="Zhao W">W Zhao</name></author><author><name sortKey="Zheng, C" uniqKey="Zheng C">C Zheng</name></author><author><name sortKey="Wang, F" uniqKey="Wang F">F Wang</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, G" uniqKey="Li G">G Li</name></author><author><name sortKey="Clercq, Ed" uniqKey="Clercq E">ED Clercq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author><author><name sortKey="Manheimer, E" uniqKey="Manheimer E">E Manheimer</name></author><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name></author><author><name sortKey="Gluud, C" uniqKey="Gluud C">C Gluud</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, T" uniqKey="Li T">T Li</name></author><author><name sortKey="Peng, T" uniqKey="Peng T">T Peng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leung, Pc" uniqKey="Leung P">PC Leung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Yh" uniqKey="Jin Y">YH Jin</name></author><author><name sortKey="Cai, L" uniqKey="Cai L">L Cai</name></author><author><name sortKey="Cheng, Zs" uniqKey="Cheng Z">ZS Cheng</name></author><author><name sortKey="Cheng, H" uniqKey="Cheng H">H Cheng</name></author><author><name sortKey="Deng, T" uniqKey="Deng T">T Deng</name></author><author><name sortKey="Fan, Yp" uniqKey="Fan Y">YP Fan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Habibzadeh, P" uniqKey="Habibzadeh P">P Habibzadeh</name></author><author><name sortKey="Stoneman, Ek" uniqKey="Stoneman E">EK Stoneman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jordan, Pc" uniqKey="Jordan P">PC Jordan</name></author><author><name sortKey="Stevens, Sk" uniqKey="Stevens S">SK Stevens</name></author><author><name sortKey="Deval, J" uniqKey="Deval J">J Deval</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Clercq, E" uniqKey="De Clercq E">E De Clercq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Cao, R" uniqKey="Cao R">R Cao</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author><author><name sortKey="Xu, M" uniqKey="Xu M">M Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, Tp" uniqKey="Sheahan T">TP Sheahan</name></author><author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name></author><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author><author><name sortKey="Gralinski, Le" uniqKey="Gralinski L">LE Gralinski</name></author><author><name sortKey="Case, Jb" uniqKey="Case J">JB Case</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holshue, Ml" uniqKey="Holshue M">ML Holshue</name></author><author><name sortKey="Debolt, C" uniqKey="Debolt C">C DeBolt</name></author><author><name sortKey="Lindquist, S" uniqKey="Lindquist S">S Lindquist</name></author><author><name sortKey="Lofy, Kh" uniqKey="Lofy K">KH Lofy</name></author><author><name sortKey="Wiesman, J" uniqKey="Wiesman J">J Wiesman</name></author><author><name sortKey="Bruce, H" uniqKey="Bruce H">H Bruce</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Cc" uniqKey="Lai C">CC Lai</name></author><author><name sortKey="Shih, Tp" uniqKey="Shih T">TP Shih</name></author><author><name sortKey="Ko, Wc" uniqKey="Ko W">WC Ko</name></author><author><name sortKey="Tang, Hj" uniqKey="Tang H">HJ Tang</name></author><author><name sortKey="Hsueh, Pr" uniqKey="Hsueh P">PR Hsueh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Savarino, A" uniqKey="Savarino A">A Savarino</name></author><author><name sortKey="Di Trani, L" uniqKey="Di Trani L">L Di Trani</name></author><author><name sortKey="Donatelli, I" uniqKey="Donatelli I">I Donatelli</name></author><author><name sortKey="Cauda, R" uniqKey="Cauda R">R Cauda</name></author><author><name sortKey="Cassone, A" uniqKey="Cassone A">A Cassone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yan, Y" uniqKey="Yan Y">Y Yan</name></author><author><name sortKey="Zou, Z" uniqKey="Zou Z">Z Zou</name></author><author><name sortKey="Sun, Y" uniqKey="Sun Y">Y Sun</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Xu, Kf" uniqKey="Xu K">KF Xu</name></author><author><name sortKey="Wei, Y" uniqKey="Wei Y">Y Wei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wong, Ck" uniqKey="Wong C">CK Wong</name></author><author><name sortKey="Lam, Cw" uniqKey="Lam C">CW Lam</name></author><author><name sortKey="Wu, Ak" uniqKey="Wu A">AK Wu</name></author><author><name sortKey="Ip, Wk" uniqKey="Ip W">WK Ip</name></author><author><name sortKey="Lee, Nl" uniqKey="Lee N">NL Lee</name></author><author><name sortKey="Chan, Ih" uniqKey="Chan I">IH Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, L" uniqKey="He L">L He</name></author><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y Ding</name></author><author><name sortKey="Zhang, Q" uniqKey="Zhang Q">Q Zhang</name></author><author><name sortKey="Che, X" uniqKey="Che X">X Che</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Shen, H" uniqKey="Shen H">H Shen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faure, E" uniqKey="Faure E">E Faure</name></author><author><name sortKey="Poissy, J" uniqKey="Poissy J">J Poissy</name></author><author><name sortKey="Goffard, A" uniqKey="Goffard A">A Goffard</name></author><author><name sortKey="Fournier, C" uniqKey="Fournier C">C Fournier</name></author><author><name sortKey="Kipnis, E" uniqKey="Kipnis E">E Kipnis</name></author><author><name sortKey="Titecat, M" uniqKey="Titecat M">M Titecat</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author><author><name sortKey="Feldmann, F" uniqKey="Feldmann F">F Feldmann</name></author><author><name sortKey="Okumura, A" uniqKey="Okumura A">A Okumura</name></author><author><name sortKey="Scott, Dp" uniqKey="Scott D">DP Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stockman, Lj" uniqKey="Stockman L">LJ Stockman</name></author><author><name sortKey="Bellamy, R" uniqKey="Bellamy R">R Bellamy</name></author><author><name sortKey="Garner, P" uniqKey="Garner P">P Garner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lansbury, L" uniqKey="Lansbury L">L Lansbury</name></author><author><name sortKey="Rodrigo, C" uniqKey="Rodrigo C">C Rodrigo</name></author><author><name sortKey="Leonardi Bee, J" uniqKey="Leonardi Bee J">J Leonardi-Bee</name></author><author><name sortKey="Nguyen Van Tam, J" uniqKey="Nguyen Van Tam J">J Nguyen-Van-Tam</name></author><author><name sortKey="Lim, Ws" uniqKey="Lim W">WS Lim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Mandourah, Y" uniqKey="Mandourah Y">Y Mandourah</name></author><author><name sortKey="Al Hameed, F" uniqKey="Al Hameed F">F Al-Hameed</name></author><author><name sortKey="Sindi, Aa" uniqKey="Sindi A">AA Sindi</name></author><author><name sortKey="Almekhlafi, Ga" uniqKey="Almekhlafi G">GA Almekhlafi</name></author><author><name sortKey="Hussein, Ma" uniqKey="Hussein M">MA Hussein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russell, Cd" uniqKey="Russell C">CD Russell</name></author><author><name sortKey="Millar, Je" uniqKey="Millar J">JE Millar</name></author><author><name sortKey="Baillie, Jk" uniqKey="Baillie J">JK Baillie</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Hung, Ifn" uniqKey="Hung I">IFN Hung</name></author><author><name sortKey="To, Kkw" uniqKey="To K">KKW To</name></author><author><name sortKey="Lee, Ck" uniqKey="Lee C">CK Lee</name></author><author><name sortKey="Lee, Kl" uniqKey="Lee K">KL Lee</name></author><author><name sortKey="Yan, Ww" uniqKey="Yan W">WW Yan</name></author><author><name sortKey="Chan, K" uniqKey="Chan K">K Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, H" uniqKey="Luo H">H Luo</name></author><author><name sortKey="Tang, Ql" uniqKey="Tang Q">QL Tang</name></author><author><name sortKey="Shang, Yx" uniqKey="Shang Y">YX Shang</name></author><author><name sortKey="Liang, Sb" uniqKey="Liang S">SB Liang</name></author><author><name sortKey="Yang, M" uniqKey="Yang M">M Yang</name></author><author><name sortKey="Robinson, N" uniqKey="Robinson N">N Robinson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tong, X" uniqKey="Tong X">X Tong</name></author><author><name sortKey="Li, A" uniqKey="Li A">A Li</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Duan, J" uniqKey="Duan J">J Duan</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Hua, C" uniqKey="Hua C">C Hua</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name></author><author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name></author><author><name sortKey="He, L" uniqKey="He L">L He</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Mm" uniqKey="Zhang M">MM Zhang</name></author><author><name sortKey="Liu, Xm" uniqKey="Liu X">XM Liu</name></author><author><name sortKey="He, L" uniqKey="He L">L He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhong, N" uniqKey="Zhong N">N Zhong</name></author><author><name sortKey="May, Rm" uniqKey="May R">RM May</name></author><author><name sortKey="Mclean, Ar" uniqKey="Mclean A">AR McLean</name></author><author><name sortKey="Pattison, J" uniqKey="Pattison J">J Pattison</name></author><author><name sortKey="Weiss, Ra" uniqKey="Weiss R">RA Weiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jsm, P" uniqKey="Jsm P">P JSM</name></author><author><name sortKey="D, P" uniqKey="D P">P D</name></author><author><name sortKey="Yuen Ky, Ea" uniqKey="Yuen Ky E">ea Yuen KY</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jr, Tmf" uniqKey="Jr T">TMF Jr</name></author><author><name sortKey="Tsang, Kwt" uniqKey="Tsang K">KWT Tsang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name></author><author><name sortKey="Nakamura, T" uniqKey="Nakamura T">T Nakamura</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Poon, Pm" uniqKey="Poon P">PM Poon</name></author><author><name sortKey="Wong, Ck" uniqKey="Wong C">CK Wong</name></author><author><name sortKey="Fung, Kp" uniqKey="Fung K">KP Fung</name></author><author><name sortKey="Fong, Cy" uniqKey="Fong C">CY Fong</name></author><author><name sortKey="Wong, El" uniqKey="Wong E">EL Wong</name></author><author><name sortKey="Lau, Jt" uniqKey="Lau J">JT Lau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hsu, Ch" uniqKey="Hsu C">CH Hsu</name></author><author><name sortKey="Hwang, Kc" uniqKey="Hwang K">KC Hwang</name></author><author><name sortKey="Chao, Cl" uniqKey="Chao C">CL Chao</name></author><author><name sortKey="Chang, Sg" uniqKey="Chang S">SG Chang</name></author><author><name sortKey="Ho, Ms" uniqKey="Ho M">MS Ho</name></author><author><name sortKey="Chou, P" uniqKey="Chou P">P Chou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cinatl, J" uniqKey="Cinatl J">J Cinatl</name></author><author><name sortKey="Morgenstern, B" uniqKey="Morgenstern B">B Morgenstern</name></author><author><name sortKey="Bauer, G" uniqKey="Bauer G">G Bauer</name></author><author><name sortKey="Chandra, P" uniqKey="Chandra P">P Chandra</name></author><author><name sortKey="Rabenau, H" uniqKey="Rabenau H">H Rabenau</name></author><author><name sortKey="Doerr, Hw" uniqKey="Doerr H">HW Doerr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, F" uniqKey="Chen F">F Chen</name></author><author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y Jiang</name></author><author><name sortKey="Kao, Ry" uniqKey="Kao R">RY Kao</name></author><author><name sortKey="Lu, Ht" uniqKey="Lu H">HT Lu</name></author><author><name sortKey="Fan, Kw" uniqKey="Fan K">KW Fan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Sq" uniqKey="Wang S">SQ Wang</name></author><author><name sortKey="Du, Qs" uniqKey="Du Q">QS Du</name></author><author><name sortKey="Zhao, K" uniqKey="Zhao K">K Zhao</name></author><author><name sortKey="Li, Ax" uniqKey="Li A">AX Li</name></author><author><name sortKey="Wei, Dq" uniqKey="Wei D">DQ Wei</name></author><author><name sortKey="Chou, Kc" uniqKey="Chou K">KC Chou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, T" uniqKey="Wu T">T Wu</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Zeng, X" uniqKey="Zeng X">X Zeng</name></author><author><name sortKey="Poole, P" uniqKey="Poole P">P Poole</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cragg, Gm" uniqKey="Cragg G">GM Cragg</name></author><author><name sortKey="Newman, Dj" uniqKey="Newman D">DJ Newman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, W" uniqKey="Luo W">W Luo</name></author><author><name sortKey="Su, X" uniqKey="Su X">X Su</name></author><author><name sortKey="Gong, S" uniqKey="Gong S">S Gong</name></author><author><name sortKey="Qin, Y" uniqKey="Qin Y">Y Qin</name></author><author><name sortKey="Liu, W" uniqKey="Liu W">W Liu</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fung, Kp" uniqKey="Fung K">KP Fung</name></author><author><name sortKey="Leung, Pc" uniqKey="Leung P">PC Leung</name></author><author><name sortKey="Tsui, Kw" uniqKey="Tsui K">KW Tsui</name></author><author><name sortKey="Wan, Cc" uniqKey="Wan C">CC Wan</name></author><author><name sortKey="Wong, Kb" uniqKey="Wong K">KB Wong</name></author><author><name sortKey="Waye, My" uniqKey="Waye M">MY Waye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Km" uniqKey="Lau K">KM Lau</name></author><author><name sortKey="Lee, Km" uniqKey="Lee K">KM Lee</name></author><author><name sortKey="Koon, Cm" uniqKey="Koon C">CM Koon</name></author><author><name sortKey="Cheung, Cs" uniqKey="Cheung C">CS Cheung</name></author><author><name sortKey="Lau, Cp" uniqKey="Lau C">CP Lau</name></author><author><name sortKey="Ho, Hm" uniqKey="Ho H">HM Ho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gong, Sj" uniqKey="Gong S">SJ Gong</name></author><author><name sortKey="Su, Xj" uniqKey="Su X">XJ Su</name></author><author><name sortKey="Yu, Hp" uniqKey="Yu H">HP Yu</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author><author><name sortKey="Qin, Yj" uniqKey="Qin Y">YJ Qin</name></author><author><name sortKey="Xu, Q" uniqKey="Xu Q">Q Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Cw" uniqKey="Lin C">CW Lin</name></author><author><name sortKey="Tsai, Fj" uniqKey="Tsai F">FJ Tsai</name></author><author><name sortKey="Tsai, Ch" uniqKey="Tsai C">CH Tsai</name></author><author><name sortKey="Lai, Cc" uniqKey="Lai C">CC Lai</name></author><author><name sortKey="Wan, L" uniqKey="Wan L">L Wan</name></author><author><name sortKey="Ho, Ty" uniqKey="Ho T">TY Ho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nguyen, Tth" uniqKey="Nguyen T">TTH Nguyen</name></author><author><name sortKey="Woo, Hj" uniqKey="Woo H">HJ Woo</name></author><author><name sortKey="Kang, Hk" uniqKey="Kang H">HK Kang</name></author><author><name sortKey="Nguyen, Vd" uniqKey="Nguyen V">VD Nguyen</name></author><author><name sortKey="Kim, Ym" uniqKey="Kim Y">YM Kim</name></author><author><name sortKey="Kim, Dw" uniqKey="Kim D">DW Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jo, S" uniqKey="Jo S">S Jo</name></author><author><name sortKey="Kim, S" uniqKey="Kim S">S Kim</name></author><author><name sortKey="Shin, Dh" uniqKey="Shin D">DH Shin</name></author><author><name sortKey="Kim, M S" uniqKey="Kim M">M-S Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jo, S" uniqKey="Jo S">S Jo</name></author><author><name sortKey="Kim, H" uniqKey="Kim H">H Kim</name></author><author><name sortKey="Kim, S" uniqKey="Kim S">S Kim</name></author><author><name sortKey="Shin, Dh" uniqKey="Shin D">DH Shin</name></author><author><name sortKey="Kim, Ms" uniqKey="Kim M">MS Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, Ms" uniqKey="Yu M">MS Yu</name></author><author><name sortKey="Lee, J" uniqKey="Lee J">J Lee</name></author><author><name sortKey="Lee, Jm" uniqKey="Lee J">JM Lee</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y Kim</name></author><author><name sortKey="Chin, Yw" uniqKey="Chin Y">YW Chin</name></author><author><name sortKey="Jee, Jg" uniqKey="Jee J">JG Jee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Cy" uniqKey="Wu C">CY Wu</name></author><author><name sortKey="Jan, Jt" uniqKey="Jan J">JT Jan</name></author><author><name sortKey="Ma, Sh" uniqKey="Ma S">SH Ma</name></author><author><name sortKey="Kuo, Cj" uniqKey="Kuo C">CJ Kuo</name></author><author><name sortKey="Juan, Hf" uniqKey="Juan H">HF Juan</name></author><author><name sortKey="Cheng, Yse" uniqKey="Cheng Y">YSE Cheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuhn, Jh" uniqKey="Kuhn J">JH Kuhn</name></author><author><name sortKey="Radoshitzky, Sr" uniqKey="Radoshitzky S">SR Radoshitzky</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Wong, Sk" uniqKey="Wong S">SK Wong</name></author><author><name sortKey="Choe, H" uniqKey="Choe H">H Choe</name></author><author><name sortKey="Farzan, M" uniqKey="Farzan M">M Farzan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Letko, M" uniqKey="Letko M">M Letko</name></author><author><name sortKey="Munster, V" uniqKey="Munster V">V Munster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Hx" uniqKey="Lin H">HX Lin</name></author><author><name sortKey="Feng, Y" uniqKey="Feng Y">Y Feng</name></author><author><name sortKey="Wong, G" uniqKey="Wong G">G Wong</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Li, B" uniqKey="Li B">B Li</name></author><author><name sortKey="Zhao, X" uniqKey="Zhao X">X Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Xt" uniqKey="Xu X">XT Xu</name></author><author><name sortKey="Chen, P" uniqKey="Chen P">P Chen</name></author><author><name sortKey="Wang, Jf" uniqKey="Wang J">JF Wang</name></author><author><name sortKey="Feng, Jn" uniqKey="Feng J">JN Feng</name></author><author><name sortKey="Zhou, H" uniqKey="Zhou H">H Zhou</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ho, T" uniqKey="Ho T">T Ho</name></author><author><name sortKey="Wu, S" uniqKey="Wu S">S Wu</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Li, C" uniqKey="Li C">C Li</name></author><author><name sortKey="Hsiang, C" uniqKey="Hsiang C">C Hsiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, Yf" uniqKey="Deng Y">YF Deng</name></author><author><name sortKey="Aluko, Re" uniqKey="Aluko R">RE Aluko</name></author><author><name sortKey="Jin, Q" uniqKey="Jin Q">Q Jin</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Yuan, Lj" uniqKey="Yuan L">LJ Yuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, S" uniqKey="Takahashi S">S Takahashi</name></author><author><name sortKey="Yoshiya, T" uniqKey="Yoshiya T">T Yoshiya</name></author><author><name sortKey="Yoshizawa Kumagaye, K" uniqKey="Yoshizawa Kumagaye K">K Yoshizawa-Kumagaye</name></author><author><name sortKey="Sugiyama, T" uniqKey="Sugiyama T">T Sugiyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Ma, X" uniqKey="Ma X">X Ma</name></author><author><name sortKey="Han, J" uniqKey="Han J">J Han</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M Zhou</name></author><author><name sortKey="Ren, H" uniqKey="Ren H">H Ren</name></author><author><name sortKey="Pan, Q" uniqKey="Pan Q">Q Pan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yi, L" uniqKey="Yi L">L Yi</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z Li</name></author><author><name sortKey="Yuan, K" uniqKey="Yuan K">K Yuan</name></author><author><name sortKey="Qu, X" uniqKey="Qu X">X Qu</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Wang, G" uniqKey="Wang G">G Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwarz, S" uniqKey="Schwarz S">S Schwarz</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K Wang</name></author><author><name sortKey="Yu, Wj" uniqKey="Yu W">WJ Yu</name></author><author><name sortKey="Sun, B" uniqKey="Sun B">B Sun</name></author><author><name sortKey="Schwarz, W" uniqKey="Schwarz W">W Schwarz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwarz, S" uniqKey="Schwarz S">S Schwarz</name></author><author><name sortKey="Sauter, D" uniqKey="Sauter D">D Sauter</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K Wang</name></author><author><name sortKey="Zhang, R" uniqKey="Zhang R">R Zhang</name></author><author><name sortKey="Sun, B" uniqKey="Sun B">B Sun</name></author><author><name sortKey="Karioti, A" uniqKey="Karioti A">A Karioti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheng, Pw" uniqKey="Cheng P">PW Cheng</name></author><author><name sortKey="Ng, Lt" uniqKey="Ng L">LT Ng</name></author><author><name sortKey="Chiang, Lc" uniqKey="Chiang L">LC Chiang</name></author><author><name sortKey="Lin, Cc" uniqKey="Lin C">CC Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pilcher, H" uniqKey="Pilcher H">H Pilcher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Cj" uniqKey="Chen C">CJ Chen</name></author><author><name sortKey="Michaelis, M" uniqKey="Michaelis M">M Michaelis</name></author><author><name sortKey="Hsu, Hk" uniqKey="Hsu H">HK Hsu</name></author><author><name sortKey="Tsai, Cc" uniqKey="Tsai C">CC Tsai</name></author><author><name sortKey="Yang, Kd" uniqKey="Yang K">KD Yang</name></author><author><name sortKey="Wu, Yc" uniqKey="Wu Y">YC Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, H" uniqKey="Lu H">H Lu</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Howard, Om" uniqKey="Howard O">OM Howard</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Oppenheim, Jj" uniqKey="Oppenheim J">JJ Oppenheim</name></author><author><name sortKey="Krakauer, T" uniqKey="Krakauer T">T Krakauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y Gao</name></author><author><name sortKey="Fang, L" uniqKey="Fang L">L Fang</name></author><author><name sortKey="Cai, R" uniqKey="Cai R">R Cai</name></author><author><name sortKey="Zong, C" uniqKey="Zong C">C Zong</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Lu, J" uniqKey="Lu J">J Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Mc" uniqKey="Chan M">MC Chan</name></author><author><name sortKey="Chan, Rw" uniqKey="Chan R">RW Chan</name></author><author><name sortKey="Mok, Ck" uniqKey="Mok C">CK Mok</name></author><author><name sortKey="Mak, Nk" uniqKey="Mak N">NK Mak</name></author><author><name sortKey="Wong, Rn" uniqKey="Wong R">RN Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y Ding</name></author><author><name sortKey="Zeng, L" uniqKey="Zeng L">L Zeng</name></author><author><name sortKey="Li, R" uniqKey="Li R">R Li</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name></author><author><name sortKey="Zhou, B" uniqKey="Zhou B">B Zhou</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dong, L" uniqKey="Dong L">L Dong</name></author><author><name sortKey="Xia, Jw" uniqKey="Xia J">JW Xia</name></author><author><name sortKey="Gong, Y" uniqKey="Gong Y">Y Gong</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name></author><author><name sortKey="Yang, H H" uniqKey="Yang H">H-H Yang</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, S" uniqKey="Li S">S Li</name></author><author><name sortKey="Chen, C" uniqKey="Chen C">C Chen</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name></author><author><name sortKey="Guo, H" uniqKey="Guo H">H Guo</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Fr" uniqKey="Chang F">FR Chang</name></author><author><name sortKey="Yen, Ct" uniqKey="Yen C">CT Yen</name></author><author><name sortKey="Ei Shazly, M" uniqKey="Ei Shazly M">M Ei-Shazly</name></author><author><name sortKey="Lin, Wh" uniqKey="Lin W">WH Lin</name></author><author><name sortKey="Yen, Mh" uniqKey="Yen M">MH Yen</name></author><author><name sortKey="Lin, Kh" uniqKey="Lin K">KH Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shen, Yc" uniqKey="Shen Y">YC Shen</name></author><author><name sortKey="Wang, Lt" uniqKey="Wang L">LT Wang</name></author><author><name sortKey="Khalil, At" uniqKey="Khalil A">AT Khalil</name></author><author><name sortKey="Chiang, Lc" uniqKey="Chiang L">LC Chiang</name></author><author><name sortKey="Cheng, Pw" uniqKey="Cheng P">PW Cheng</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Han, Yy" uniqKey="Han Y">YY Han</name></author><author><name sortKey="Zhao, Mr" uniqKey="Zhao M">MR Zhao</name></author><author><name sortKey="Shi, B" uniqKey="Shi B">B Shi</name></author><author><name sortKey="Song, Zh" uniqKey="Song Z">ZH Song</name></author><author><name sortKey="Zhou, Sp" uniqKey="Zhou S">SP Zhou</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, Yg" uniqKey="Zhu Y">YG Zhu</name></author><author><name sortKey="Deng, Zw" uniqKey="Deng Z">ZW Deng</name></author><author><name sortKey="Liu, Lh" uniqKey="Liu L">LH Liu</name></author><author><name sortKey="Liu, Xh" uniqKey="Liu X">XH Liu</name></author><author><name sortKey="Li, Xz" uniqKey="Li X">XZ Li</name></author><author><name sortKey="Chen, Wh" uniqKey="Chen W">WH Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, X" uniqKey="Xu X">X Xu</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Li, Xx" uniqKey="Li X">XX Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Tian, Ss" uniqKey="Tian S">SS Tian</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author><author><name sortKey="Zhang, Wd" uniqKey="Zhang W">WD Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yao, Kt" uniqKey="Yao K">KT Yao</name></author><author><name sortKey="Liu, My" uniqKey="Liu M">MY Liu</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Huang, Jh" uniqKey="Huang J">JH Huang</name></author><author><name sortKey="Cai, Hb" uniqKey="Cai H">HB Cai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lv, Rb" uniqKey="Lv R">RB Lv</name></author><author><name sortKey="Wang, Wj" uniqKey="Wang W">WJ Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Jw" uniqKey="Zhang J">JW Zhang</name></author><author><name sortKey="Hu, X" uniqKey="Hu X">X Hu</name></author><author><name sortKey="Jin, Pf" uniqKey="Jin P">PF Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Yang, D" uniqKey="Yang D">D Yang</name></author><author><name sortKey="Shen, W" uniqKey="Shen W">W Shen</name></author><author><name sortKey="Dong, Hf" uniqKey="Dong H">HF Dong</name></author><author><name sortKey="Wang, Jm" uniqKey="Wang J">JM Wang</name></author><author><name sortKey="Oppenheim, Jj" uniqKey="Oppenheim J">JJ Oppenheim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Mellon, Rd" uniqKey="Mellon R">RD Mellon</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L Yang</name></author><author><name sortKey="Dong, H" uniqKey="Dong H">H Dong</name></author><author><name sortKey="Oppenheim, Jj" uniqKey="Oppenheim J">JJ Oppenheim</name></author><author><name sortKey="Howard, Om" uniqKey="Howard O">OM Howard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Beutler, Ja" uniqKey="Beutler J">JA Beutler</name></author><author><name sortKey="Mccloud, Tg" uniqKey="Mccloud T">TG McCloud</name></author><author><name sortKey="Loehfelm, A" uniqKey="Loehfelm A">A Loehfelm</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L Yang</name></author><author><name sortKey="Dong, Hf" uniqKey="Dong H">HF Dong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L Yang</name></author><author><name sortKey="Zhang, N" uniqKey="Zhang N">N Zhang</name></author><author><name sortKey="Turpin, Ja" uniqKey="Turpin J">JA Turpin</name></author><author><name sortKey="Buckheit, Rw" uniqKey="Buckheit R">RW Buckheit</name></author><author><name sortKey="Osterling, C" uniqKey="Osterling C">C Osterling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Oppenheim, Jj" uniqKey="Oppenheim J">JJ Oppenheim</name></author><author><name sortKey="Howard, Om" uniqKey="Howard O">OM Howard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Murakami, T" uniqKey="Murakami T">T Murakami</name></author><author><name sortKey="Oppenheim, Jj" uniqKey="Oppenheim J">JJ Oppenheim</name></author><author><name sortKey="Howard, Om" uniqKey="Howard O">OM Howard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, J" uniqKey="He J">J He</name></author><author><name sortKey="He, Zd" uniqKey="He Z">ZD He</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Yb" uniqKey="Chen Y">YB Chen</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="Qiao, Lf" uniqKey="Qiao L">LF Qiao</name></author><author><name sortKey="Li, Ys" uniqKey="Li Y">YS Li</name></author><author><name sortKey="Yang, Gt" uniqKey="Yang G">GT Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Xj" uniqKey="Chang X">XJ Chang</name></author><author><name sortKey="Xiao, W" uniqKey="Xiao W">W Xiao</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name></author><author><name sortKey="Chang, Yp" uniqKey="Chang Y">YP Chang</name></author><author><name sortKey="Chen, Cm" uniqKey="Chen C">CM Chen</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zou, Hm" uniqKey="Zou H">HM Zou</name></author><author><name sortKey="He, Tz" uniqKey="He T">TZ He</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author><author><name sortKey="Du, Q" uniqKey="Du Q">Q Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, Awt" uniqKey="Ng A">AWT Ng</name></author><author><name sortKey="Poon, Sl" uniqKey="Poon S">SL Poon</name></author><author><name sortKey="Huang, Mn" uniqKey="Huang M">MN Huang</name></author><author><name sortKey="Lim, Jq" uniqKey="Lim J">JQ Lim</name></author><author><name sortKey="Boot, A" uniqKey="Boot A">A Boot</name></author><author><name sortKey="Yu, W" uniqKey="Yu W">W Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeng, Zp" uniqKey="Zeng Z">ZP Zeng</name></author><author><name sortKey="Jiang, Jg" uniqKey="Jiang J">JG Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fugh Berman, A" uniqKey="Fugh Berman A">A Fugh-Berman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Ls" uniqKey="Liu L">LS Liu</name></author><author><name sortKey="Lei, N" uniqKey="Lei N">N Lei</name></author><author><name sortKey="Lin, Q" uniqKey="Lin Q">Q Lin</name></author><author><name sortKey="Wang, Wl" uniqKey="Wang W">WL Wang</name></author><author><name sortKey="Yan, Hw" uniqKey="Yan H">HW Yan</name></author><author><name sortKey="Duan, Xh" uniqKey="Duan X">XH Duan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fu, Yj" uniqKey="Fu Y">YJ Fu</name></author><author><name sortKey="Yan, Yq" uniqKey="Yan Y">YQ Yan</name></author><author><name sortKey="Qin, Hq" uniqKey="Qin H">HQ Qin</name></author><author><name sortKey="Wu, S" uniqKey="Wu S">S Wu</name></author><author><name sortKey="Shi, Ss" uniqKey="Shi S">SS Shi</name></author><author><name sortKey="Zheng, X" uniqKey="Zheng X">X Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Jt" uniqKey="Lau J">JT Lau</name></author><author><name sortKey="Leung, Pc" uniqKey="Leung P">PC Leung</name></author><author><name sortKey="Wong, El" uniqKey="Wong E">EL Wong</name></author><author><name sortKey="Fong, C" uniqKey="Fong C">C Fong</name></author><author><name sortKey="Cheng, Kf" uniqKey="Cheng K">KF Cheng</name></author><author><name sortKey="Zhang, Sc" uniqKey="Zhang S">SC Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, Cy" uniqKey="Du C">CY Du</name></author><author><name sortKey="Zheng, Ky" uniqKey="Zheng K">KY Zheng</name></author><author><name sortKey="Bi, Cw" uniqKey="Bi C">CW Bi</name></author><author><name sortKey="Dong, Tt" uniqKey="Dong T">TT Dong</name></author><author><name sortKey="Lin, H" uniqKey="Lin H">H Lin</name></author><author><name sortKey="Tsim, Kw" uniqKey="Tsim K">KW Tsim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, J" uniqKey="Gao J">J Gao</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author><author><name sortKey="Shao, X" uniqKey="Shao X">X Shao</name></author><author><name sortKey="Jin, Y" uniqKey="Jin Y">Y Jin</name></author><author><name sortKey="Lu, Xw" uniqKey="Lu X">XW Lu</name></author><author><name sortKey="Ge, Jf" uniqKey="Ge J">JF Ge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name></author><author><name sortKey="Zhou, W" uniqKey="Zhou W">W Zhou</name></author><author><name sortKey="Gao, S" uniqKey="Gao S">S Gao</name></author><author><name sortKey="Lin, H" uniqKey="Lin H">H Lin</name></author><author><name sortKey="Ye, S" uniqKey="Ye S">S Ye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiao, Gl" uniqKey="Xiao G">GL Xiao</name></author><author><name sortKey="Song, K" uniqKey="Song K">K Song</name></author><author><name sortKey="Yuan Cj, Ea" uniqKey="Yuan Cj E">ea Yuan CJ</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bao, L" uniqKey="Bao L">L Bao</name></author><author><name sortKey="J, M" uniqKey="J M">M J</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, De" uniqKey="Kim D">DE Kim</name></author><author><name sortKey="Min, Js" uniqKey="Min J">JS Min</name></author><author><name sortKey="Jang, Ms" uniqKey="Jang M">MS Jang</name></author><author><name sortKey="Lee, Jy" uniqKey="Lee J">JY Lee</name></author><author><name sortKey="Shin, Ys" uniqKey="Shin Y">YS Shin</name></author><author><name sortKey="Song, Jh" uniqKey="Song J">JH Song</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Biol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int. J. Biol. Sci</journal-id><journal-id journal-id-type="publisher-id">ijbs</journal-id><journal-title-group><journal-title>International Journal of Biological Sciences</journal-title></journal-title-group><issn pub-type="epub">1449-2288</issn><publisher><publisher-name>Ivyspring International Publisher</publisher-name><publisher-loc>Sydney</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32226288</article-id><article-id pub-id-type="pmc">7098036</article-id><article-id pub-id-type="doi">10.7150/ijbs.45538</article-id><article-id pub-id-type="publisher-id">ijbsv16p1708</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Yang</given-names></name><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Islam</surname><given-names>Md Sahidul</given-names></name><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jin</given-names></name></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Yuan</given-names></name></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Xin</given-names></name><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib></contrib-group><aff>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China</aff><author-notes><corresp id="FNA_envelop">✉ Corresponding author: Prof. Xin Chen, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR 999078, China. Tel.: (853) 8822 4513; Fax: (853) 2884 1358. E-mail address: <email>xchen@um.edu.mo</email>; ORCID: <ext-link ext-link-type="uri" xlink:href="http://orcid.org/0000-0002-2628-4027">http://orcid.org/0000-0002-2628-4027</ext-link></corresp><fn fn-type="equal" id="FNA_star"><p>*These authors have contributed equally to this work.</p></fn><fn fn-type="COI-statement"><p>Competing Interests: The authors have declared that no competing interest exists.</p></fn></author-notes><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>15</day><month>3</month><year>2020</year></pub-date><volume>16</volume><issue>10</issue><fpage>1708</fpage><lpage>1717</lpage><history><date date-type="received"><day>2</day><month>3</month><year>2020</year></date><date date-type="accepted"><day>8</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>© The author(s)</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>). See <ext-link ext-link-type="uri" xlink:href="http://ivyspring.com/terms">http://ivyspring.com/terms</ext-link> for full terms and conditions.</license-p></license></permissions><abstract><p>Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.</p></abstract><kwd-group><kwd>SARS-CoV-2</kwd><kwd>Traditional Chinese Medicine (TCM)</kwd><kwd>coronavirus pneumonia</kwd></kwd-group></article-meta></front><body><sec sec-type="intro"><title>Introduction</title><p>In December 2019, there was an outbreak of unexplainable pneumonia in Wuhan city, Hubei province, China <xref rid="B1" ref-type="bibr">1</xref>. By Jan 7, 2020, it was confirmed that a new type of coronavirus named SARS-CoV-2 (formerly named as 2019-nCoV) had emerged <xref rid="B2" ref-type="bibr">2</xref>. The World Health Organization (WHO) named the Wuhan pneumonia as Coronavirus Disease-2019 (COVID-19) on Feb 11, 2020 <xref rid="B3" ref-type="bibr">3</xref>. The COVID-19 patients showed typical respiratory symptom (such as cough, fever, and lung damage) and some other symptoms such as fatigue, myalgia, and diarrhea <xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B5" ref-type="bibr">5</xref>. As of February 17, 2020, a total of 73,332 cases of the SARS-CoV-2 infected pneumonia has been reported in China and 25 other countries, of which 72,528 cases was found in China <xref rid="B6" ref-type="bibr">6</xref>. Due to the rapid spread of SARS-CoV-2 through human-to-human transmission, the cases currently continue to rise. SARS-CoV-2 extracted from patients with pneumonia in Wuhan is an enveloped single stranded RNA-type beta-coronavirus <xref rid="B7" ref-type="bibr">7</xref>. The genome sequences of SARS-CoV-2 shared 79.5% sequence identity to severe acute respiratory syndrome-related coronaviruses (SARS-CoV) <xref rid="B8" ref-type="bibr">8</xref>, <xref rid="B9" ref-type="bibr">9</xref>. In addition, the spike (S) protein of SARS-CoV-2 and SARS-CoV enters human alveolar epithelial cells through binding angiotensin- converting enzyme 2 (ACE2) receptor <xref rid="B8" ref-type="bibr">8</xref>.</p><p>COVID-19 can be diagnosed by either chest CT radiography or a laboratory testing. Unfortunately, specific antiviral drugs or vaccines currently have not been available for the treatment <xref rid="B10" ref-type="bibr">10</xref>, <xref rid="B11" ref-type="bibr">11</xref>. According to the current clinical guideline in China and the experiences in the treatment of SARS or Middle East Respiratory Syndrome (MERS) patients, both conventional medicine and traditional Chinese medicine (TCM) are used for the treatment of patients with infection of SARS-CoV-2 in China <xref rid="B12" ref-type="bibr">12</xref>-<xref rid="B14" ref-type="bibr">14</xref>. This review mainly focuses on the discussion of TCM usage in the treatment of COVID-19 patients, in the context of current conventional management. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV <xref rid="B8" ref-type="bibr">8</xref>, <xref rid="B9" ref-type="bibr">9</xref>, and widely usage of TCM in the treatment of patients infected with SARS-CoV in 2002-2003 <xref rid="B15" ref-type="bibr">15</xref>, the clinical evidence showing the efficacy and safety of TCM in the treatment of patients with the emerging coronaviral will be summarized and analyzed, including the laboratory studies that provide an insight into molecular basis of therapeutic benefits.</p></sec><sec><title>Conventional treatment of SARS-CoV-2: is there a room for Chinese medicine?</title><p>Due to the absence of a specific antiviral therapeutics and vaccine, main treatment strategy for COVID-19 is supportive care, which is supplemented by the combination of broad-spectrum antibiotics, antivirals, corticosteroids and convalescent plasma <xref rid="B16" ref-type="bibr">16</xref> (Table <xref rid="T1" ref-type="table">1</xref>). HIV protease inhibitors ritonavir and lopinavir have been used, typically in combination with appropriate antibiotics or with IFNα-2b, in the treatment of SARS-CoV-2 infected patients <xref rid="B7" ref-type="bibr">7</xref>, <xref rid="B17" ref-type="bibr">17</xref>. Nucleoside analogs such as ribavirin <xref rid="B12" ref-type="bibr">12</xref> may be potentially beneficial for the treatment of COVID-19, since ribavirin was approved for treating respiratory syncytial virus (RSV) infection <xref rid="B18" ref-type="bibr">18</xref> and used extensively during the SARS and MERS outbreak <xref rid="B10" ref-type="bibr">10</xref>. However, ribavirin had severe side effects such as anemia <xref rid="B18" ref-type="bibr">18</xref> and whether it had sufficient antiviral activity against SARS-CoV-2 is unclear. Nucleoside analogs favipiravir (T-705) can effectively inhibit the activity of RNA polymerase of RNA viruses such as influenza <xref rid="B19" ref-type="bibr">19</xref>. A recent <italic>in vitro</italic> study found that it had the anti-SARS-CoV-2 activity <xref rid="B20" ref-type="bibr">20</xref>, but the <italic>in vivo</italic> effect remains elusive. Remdesivir may be the most promising antiviral drug for treating COVID-19. It has <italic>in vitro</italic> and <italic>in vivo</italic> antiviral activity against a wide array of RNA viruses including SARS and MERS <xref rid="B21" ref-type="bibr">21</xref>, and could decrease viral loads and pathology of lungs in animal models <xref rid="B22" ref-type="bibr">22</xref>. A study showed remdesivir markedly inhibited the infection of SARS-CoV-2 in Vero E6 cells <xref rid="B20" ref-type="bibr">20</xref>, and most symptoms of the first US patient infected with SARS-CoV-2 had resolved swiftly after intravenous administration with remdesivir <xref rid="B23" ref-type="bibr">23</xref>. Currently, it is under clinical trial to evaluate the safety and efficacy of intravenous remdesivir for patients with SARS-CoV-2 infection <xref rid="B24" ref-type="bibr">24</xref>. Oral oseltamivir has been used for the treatment of the cases with SARS-CoV-2 <xref rid="B7" ref-type="bibr">7</xref>, while its efficacy currently remains uncertain.</p><p>Host-targeted small molecules approved for other human diseases may modulate the virus-host interactions of SARS-CoV-2. Chloroquine, a potential broad-spectrum antiviral drug <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>, was shown by a recent study had anti-SARS-CoV-2 activity <xref rid="B20" ref-type="bibr">20</xref>. Its clinical efficacy is under study in an open-label trial (ChiCTR2000029609) <xref rid="B12" ref-type="bibr">12</xref>. IFNα (5 million U) atomization inhalation was recommended as antiviral therapy to treat SARS-CoV-2 <xref rid="B16" ref-type="bibr">16</xref>. A trial testing IFNα-2b combination of the approved anti-HCV inhibitors has been initiated <xref rid="B17" ref-type="bibr">17</xref>, however, whether it could act synergistically against SARS-CoV-2 is unclear.</p><p>Corticosteroids were frequently used to suppress the elevated cytokine levels in patients with SARS-CoV <xref rid="B27" ref-type="bibr">27</xref>, <xref rid="B28" ref-type="bibr">28</xref> and MERS-CoV <xref rid="B29" ref-type="bibr">29</xref>, <xref rid="B30" ref-type="bibr">30</xref>. However, there are no evidence showing that the mortality of SARS and MERS patients was reduced by the treatment with corticosteroids, while the clearance of viral was delayed by such treatment <xref rid="B31" ref-type="bibr">31</xref>-<xref rid="B33" ref-type="bibr">33</xref>. Consequently, corticosteroids are not suggested to systemically use in SARS-CoV-2 infected patients <xref rid="B34" ref-type="bibr">34</xref>, <xref rid="B35" ref-type="bibr">35</xref>.</p><p>Previously, it was shown that, either in severe influenza or SARS-CoV infection, convalescent plasma treatment could significantly decrease viral load and reduce the mortality <xref rid="B31" ref-type="bibr">31</xref>, <xref rid="B36" ref-type="bibr">36</xref>. Convalescent plasma has been used for severe SARS-CoV-2 infection in China <xref rid="B22" ref-type="bibr">22</xref>, although promising, the efficacy and safety need to be carefully further evaluated.</p><p>Consistent with previous analysis, WHO also concluded "to date, there is no specific medicine recommended to prevent or treat SARS-CoV-2" <xref rid="B37" ref-type="bibr">37</xref>. TCM has been used in control of infectious diseases for thousands of years. There is a clear room for the intervention of TCM as a complementary therapy for COVID-19 patients. It is reported that the patients with SARS-CoV infection have benefited from TCM treatment <xref rid="B38" ref-type="bibr">38</xref>, including amelioration of side effect of conventional therapeutics <xref rid="B39" ref-type="bibr">39</xref>, <xref rid="B40" ref-type="bibr">40</xref>. Based on these factors, there is a general expectation that TCM would be a valuable weapon in the armory against SARS-CoV-2.</p></sec><sec><title>Traditional Chinese Medicine in the treatment of patients infected with SARS-CoV: clinical evidence</title><p>Application of TCM in the treatment of SARS-CoV-2 is largely inspired by the treatment of SARS caused by outbreak of SARS coronavirus (SARS-CoV) in the late of 2002 in the Guangdong Province of China which spread rapidly during the 2003, with the cumulative number worldwide of over 8,000 <xref rid="B41" ref-type="bibr">41</xref>-<xref rid="B43" ref-type="bibr">43</xref>. Ranging from case reports, case series, controlled observational studies and randomized clinical trials, clinical studies aiming to examine the effect of TCM on SARS have been carried out and reported. There are quite compelling evidences support the notion that TCM has beneficial effect in the treatment or prevention of SARS. For example, the rate of fatality in Hong Kong and Singapore was approximately 18%, while the rate for Beijing was initially more than 52% until the 5<sup>th</sup> of May and decreased gradually to 4%-1% after the 20<sup>th</sup> of May in 2003. The dramatic reduced fatality from late May in Beijing was believed to be associated with the use of TCM as a supplement to the conventional therapy <xref rid="B44" ref-type="bibr">44</xref>. Lau and colleagues reported that, during SARS outbreak, 1063 volunteers including 926 hospital workers and 37 laboratory technicians working in high-risk virus laboratories used a TCM herbal extract, namely <italic>Sang Ju Yin</italic> plus <italic>Yu Ping Feng San</italic>. Compared with the 0.4% of infection in the control group, none of TCM users infected. Furthermore, there was some evidence that <italic>Sang Ju Yin</italic> plus <italic>Yu Ping Feng San</italic> could modulate T cells in a manner to enhance host defense capacity <xref rid="B45" ref-type="bibr">45</xref>, <xref rid="B46" ref-type="bibr">46</xref>. In a controlled clinical study, the supplementary treatment with TCM resulted in marked improvement of symptoms and shortened the disease course <xref rid="B47" ref-type="bibr">47</xref>. The clinical beneficial effect of TCM appears to be supported by laboratory studies. For example, a high-profile research published in the <italic>Lancet</italic> reported that glycyrrhizin, a major active constituent <italic>liquorice root</italic> which is the most frequently used Chinese herb, potently inhibited the replication of clinical isolates of SARS virus <xref rid="B48" ref-type="bibr">48</xref>. Another independent study confirmed the antivirus activity of glycyrrhizin by plaque reduction assays and this study found that another Chinese herbal compound baicalin also had the anti-SARS activity <xref rid="B49" ref-type="bibr">49</xref>. Furthermore, Wang <italic>et al</italic>. found MOL376, a compound derived from TCM, may become a lead compound for SARS therapy by inhibition of cathepsin L, a target for the treatment of SARS <xref rid="B50" ref-type="bibr">50</xref>.</p><p>There is a myriad of literature on TCM treatments for SARS published after the SARS epidemic in China. A critical analysis of these publications would be useful to confirm the beneficial effect of TCM. Liu <italic>et al.</italic> systematically reviewed eight randomized controlled trials, and concluded that, by combination with conventional medicine, TCM showed the beneficial effects such as decrease of mortality and relief of symptom, as well as control of fungal infections in patients with SARS. However, the evidence is not sufficient enough due to the poor quality of methodology used in the trials <xref rid="B13" ref-type="bibr">13</xref>. Leung analyzed 90 peer-reviewed papers with reasonable quality from 130 publications and concluded that TCM used together with conventional treatment had some positive effects, including better control of fever, quicker clearance of chest infection and other symptoms. However, such beneficial effect of TCM is not conclusive and more high-quality clinical studies are required <xref rid="B15" ref-type="bibr">15</xref>. In another thorough literature analysis, Liu and colleagues concluded that there was no benefit of adjuvant treatment with TCM in terms of mortality <xref rid="B39" ref-type="bibr">39</xref>. Due to the lack of high quality TCM trials and biases that influenced the validity of results, Wu and colleagues suggested to re-run clinical trials of TCM for the treatment of acute respiratory tract infections (ARTIs) <xref rid="B51" ref-type="bibr">51</xref>.</p></sec><sec><title>Identification of anti-novel coronaviral compound from Traditional Chinese Medicine</title><p>Natural products used in TCM remains to be a wealthy source for the identification of novel therapeutic agents for the treatment of human diseases <xref rid="B52" ref-type="bibr">52</xref>. In the past decade, scientists have made a considerable effort to identify multiple component herbal formulae in TCM with anti-SARS-CoV activity (Table <xref rid="T2" ref-type="table">2</xref>). Further identification of chemical entities contained in TCM herbs responsible for the anti-SARS- CoV effect was also pursued (Table <xref rid="T3" ref-type="table">3</xref>). Due to the homology of SARS-CoV and SARS-CoV-2, these previous studies may shed light on the naturally occurring compounds with the capacity to inhibit SARS-CoV-2.</p><p>3- chymotrypsin-like protease (3CLpro) is vital for replication of virus, and thus represents a promising drug target for the development of therapeutics agents for SARS-CoV as well as other human coronaviruses including SARS-CoV-2. It was reported that following TCM herbal extracts had the capacity to inhibit the enzymatic activity of SARS 3CLpro: Chinese <italic>Rhubarb</italic> extracts (IC50: 13.76 ± 0.03 μg/mL) <xref rid="B53" ref-type="bibr">53</xref>, water extract of <italic>Houttuynia cordata</italic><xref rid="B54" ref-type="bibr">54</xref>, <xref rid="B55" ref-type="bibr">55</xref><italic>,</italic> flavonoid extracted from<italic> litchi</italic> seeds <xref rid="B56" ref-type="bibr">56</xref> and beta-sitosterol (IC50: 1210µM) extracted from the root extract of <italic>Isatis indigotica</italic><xref rid="B57" ref-type="bibr">57</xref>. Further, following herb-derived naturally occurring compounds including sinigrin (IC50: 217µM), indigo (IC50: 752µM), aloe-emodin (IC50: 366 µM), hesperetin (IC50:8.3 µM) <xref rid="B57" ref-type="bibr">57</xref>, quercetin (IC50: 73µM), epigallocatechin gallate (IC50: 73µM), gallocatechin gallate (IC50: 47 µM) <xref rid="B58" ref-type="bibr">58</xref>, herbacetin, rhoifolin and pectolinarin <xref rid="B59" ref-type="bibr">59</xref> were able to inhibit the SARS 3CLpro activity. Moreover, the flavonoids namely herbacetin, isobavaschalcone, quercetin 3‐β‐D‐glucoside, and helichrysetin had the potential to block the enzymatic activity of MERS‐CoV 3CL protease <xref rid="B60" ref-type="bibr">60</xref>.</p><p>The helicase protein is also considered as a potential target for the development of anti-HCoV (human coronavirus) agents. Yu <italic>et al.</italic> reported scutellarein and myricetin potently inhibited the nsP13 (SARS-CoV helicase protein) <italic>in vitro</italic> by affecting the ATPase activity <xref rid="B61" ref-type="bibr">61</xref>. The RNA- dependent RNA polymerase (RdRp), a key enzyme responsible for both positive and negative-strand RNA synthesis, also represents another potential druggable target. It was shown that the extracts of <italic>Kang Du Bu Fei Tang</italic> (IC50:471.3 µg/mL), <italic>Sinomenium acutum</italic> (IC50:198.6 µg/mL), <italic>Coriolus versicolor</italic> (IC50:108.4 µg/mL) and <italic>Ganoderma lucidum</italic> (IC50:41.9 µg/mL) inhibited SARS-CoV RdRp in a dose- dependent manner <xref rid="B54" ref-type="bibr">54</xref>. Wu <italic>et al.</italic> performed large- scale screening of existing drugs, natural products, and synthetic compounds (>10000 compounds) to identify effective anti-SARS-CoV agents through a cell-based assay with SARS virus and Vero E6 cells <xref rid="B62" ref-type="bibr">62</xref>. They found that ginsenoside-Rb1 isolated from <italic>Panax ginseng</italic>, aescin isolated from the horse chestnut tree, reserpine contained in the genus <italic>Rauwolfia</italic> and extracts of <italic>eucalyptus</italic> and <italic>Lonicera japonica</italic> inhibited SARS-CoV replication at non-toxic concentrations <xref rid="B62" ref-type="bibr">62</xref>.</p><p>Same as SARS-CoV and HCoV-NL63, SARS-CoV-2 uses host receptor ACE2 for the cellular entrance <xref rid="B63" ref-type="bibr">63</xref>-<xref rid="B66" ref-type="bibr">66</xref>. Therefore, TCM with the capacity to target ACE2 holds the promise to prevent the infection of SARS-CoV-2. Emodin from genus <italic>Rheum</italic> and <italic>Polygonum</italic><xref rid="B67" ref-type="bibr">67</xref>, baicalin from in <italic>Scutellaria baicalensis</italic><xref rid="B44" ref-type="bibr">44</xref>, <xref rid="B68" ref-type="bibr">68</xref>, nicotianamine from foodstuff (especially “soybean ACE2 inhibitor (ACE2iSB)”) <xref rid="B69" ref-type="bibr">69</xref>, scutellarin <xref rid="B70" ref-type="bibr">70</xref>, tetra-<italic>O</italic>-galloyl-β-D-glucose (TGG) from <italic>Galla chinensis</italic> and luteolin from <italic>Veronicalina riifolia</italic><xref rid="B71" ref-type="bibr">71</xref> markedly inhibited the interaction of SARS-CoV S-protein and ACE2. However, the anti-SARS-CoV activity of these compounds remain to be evaluated. In addition, inhibition of the 3a ion channel by emodin <xref rid="B72" ref-type="bibr">72</xref> or kaempferol derivatives- juglanin <xref rid="B73" ref-type="bibr">73</xref> could potentially prevent the viral release from the infected cells. Saikosaponins <xref rid="B74" ref-type="bibr">74</xref>, glycyrrhizin <xref rid="B48" ref-type="bibr">48</xref>, <xref rid="B75" ref-type="bibr">75</xref>, quercetin and TSL-1 extracted from <italic>Toona sinensis</italic> Roem <xref rid="B76" ref-type="bibr">76</xref> purportedly had potent anti-SARS-CoV effects by inhibition of viral cellular entry, adsorption, and penetration.</p><p>Overwhelming inflammatory responses are attributable to the deaths of patients with infection of SARS-CoV, or MERS-CoV, or COVID-19. Thus, anti-inflammatory agents presumably could reduce the severity and mortality rate <xref rid="B77" ref-type="bibr">77</xref>. <italic>Shuang Huang Lian,</italic> a TCM herbal product prepared from <italic>Lonicerae japonicae</italic> Flos, <italic>Scutellariae radix</italic> and <italic>Fructus Forsythiae,</italic> purportedly had the activity to inhibit SARS-CoV-2 <xref rid="B78" ref-type="bibr">78</xref>. Interestingly, We have shown that this herbal preparation potently inhibited staphylococcal toxic shock syndrome toxin 1 (TSST-1)-induced production of cytokines (IL-1β, IL-6, TNF-α, IFN-γ) and chemokines (MIP-1α, MIP-1β and MCP-1) by peripheral blood mononuclear cell (PBMC) <xref rid="B79" ref-type="bibr">79</xref>. In line with our results, this herbal product was shown to markedly reduced the transcriptional and translational levels of inflammatory cytokines TNF-α, IL-1β, and IL-6 in lipopolysaccharide-stimulated murine alveolar macrophages <xref rid="B80" ref-type="bibr">80</xref>. Indirubin is an active ingredient of a TCM preparation <italic>Dang Gui Long Hui Pill,</italic> had strong antiviral and immunomodulatory effects, as shown by a study based on the observation of influenza H5N1 virus-infected human macrophages and type-I alveolar epithelial cells <xref rid="B81" ref-type="bibr">81</xref>. <italic>Lian Hua Qing Wen Capsule</italic> was reported to have <italic>in vitro</italic> activity in inhibition of propagation of various influenza viruses. This TCM herbal product not only blocked the early stages of influenza virus infection but also inhibited virus-induced gene expression of IL-6, IL-8, TNF-a, IP-10, and MCP-1 <xref rid="B82" ref-type="bibr">82</xref>. Additionally, a study by Dong <italic>et al</italic>. reported that the levels of IL-8, TNF-α, IL-17, and IL-23 in the sputum and of IL-8 and IL-17 in the blood were markedly decreased after <italic>Lian Hua Qing Wen Capsule</italic> treatment in patients with acute exacerbation of chronic obstructive pulmonary disease <xref rid="B83" ref-type="bibr">83</xref>. A self-control study by Poon <italic>et al.</italic> showed that the administration of the TCM herbal formulas (<italic>Sang Ju Yin</italic> and <italic>Yu Ping Feng San</italic>) may have beneficial immunomodulatory effects for the prevention of viral infections including SARS-CoV <xref rid="B46" ref-type="bibr">46</xref>.</p><p>Moreover, a number of anti-coronaviral agents have been identified from TCM herbs, although the mechanisms of action have not yet been elucidated. For example, extracts from <italic>Lycoris radiata</italic>, <italic>Artemisia annua</italic>, <italic>Pyrrosia lingua</italic>, and<italic> Lindera aggregate</italic> possessed the anti-SARS‑CoV activity <xref rid="B84" ref-type="bibr">84</xref>, 3β-Friedelanol isolated from <italic>Euphorbia neriifolia</italic><xref rid="B85" ref-type="bibr">85</xref>, Blancoxanthone isolated from the roots of <italic>Calophyllum blancoi</italic><xref rid="B86" ref-type="bibr">86</xref> exhibited anti-HCoV-229E activity.</p></sec><sec><title>Traditional Chinese Medicine used in the treatment of SARS-CoV-2-infected patients: the current situations</title><p>TCM is highly valued by the government of China in their campaign to contain and eradiate SARS-CoV-2. For example, Health Commission in 26 provinces have officially declared that TCM should be used in combination with conventional medicine in the treatment of COVID-19 patients. On 17, February, National Health Commission (NHC) of the People's Republic of China reported that 60,107 confirmed COVID-19 patients (85.20% of total confirmed cases) had been treated with TCM <xref rid="B87" ref-type="bibr">87</xref>. As for March 1, 2020, a total of 303 ongoing clinical trials aiming to evaluate the efficacy and safety of treatments for CoV-19 patients have been launched in China. Among them, 50 trials (16.5%) are about the use of TCM, including 14 cases (4.6%) to examine the effect of combined treatment with TCM and Western medicine. In 22 TCM trials (7.3%), the effect of self-made herbal preparations such as <italic>Xin Guan-1 Formula</italic>, <italic>Xin Guan-2 Formula</italic> and <italic>Qing Yi-4</italic> are examined. In another 14 TCM trials (4.6%), commercially available TCM products such as <italic>Tan Re Qing Injection</italic> and<italic> Lian Hua Qing Wen Capsule</italic> are studied (Table <xref rid="T4" ref-type="table">4</xref>).</p><p>To date, NHC has published 6 editions Guidelines of Diagnosis and Treatment for COVID-19 <xref rid="B88" ref-type="bibr">88</xref>. Since the fourth versions, different herbal medicines used in TCM system has been recommended for the treatment of COVID-19, based on the stage of disease and symptom differentiation <xref rid="B89" ref-type="bibr">89</xref>. According to the latest edition of Guideline <xref rid="B88" ref-type="bibr">88</xref>, following multiple component Chinese herbal products are recommended for the patients in the medical observation period, presumably as a preventive measure: <italic>Huo Xiang Zheng Qi Shui</italic>, <italic>Lian Hua Qing Wen Capsule</italic>, S<italic>hu Feng Jie Du Capsule</italic> and <italic>Jin Hua Qing Gan Granule</italic>. In the clinical treatment period, <italic>Qing Fei Pai Du Tang</italic>, <italic>Xi Yan Ping Injection</italic>, <italic>Xue Bi Jing injection</italic>, <italic>Re Du Ning Injection, Tan Re Qing Injection</italic>, <italic>Xing Nao Jing Injection</italic> and some other Chinese medicine formulae should be selected <xref rid="B90" ref-type="bibr">90</xref>. In addition, for the patients in critical condition, <italic>Shen Fu Injection</italic>, <italic>Sheng Mai Injection</italic>, <italic>Shen Mai Injection</italic>, <italic>Su He Xiang Pill</italic> and <italic>An Gong Niu Huang Pill</italic> should be administered (Table <xref rid="T5" ref-type="table">5</xref>).</p><p>Through analysis of the frequency of TCM used in 23 provinces, Luo, et al. <xref rid="B37" ref-type="bibr">37</xref> concluded that <italic>Astragalus membranaceus, Glycyrrhizae uralensis, Saposhnikoviae divaricata, Rhizoma Atractylodis Macrocephalae, Lonicerae Japonicae Flos, Fructus forsythia, Atractylodis Rhizoma, Radix platycodonis, Agastache rugosa</italic>, and <italic>Cyrtomium fortune J. Sm</italic> were 10 most commonly used Chinese herbs in the treatment of COVID-19. Xu, <italic>et al.</italic><xref rid="B91" ref-type="bibr">91</xref> reported that <italic>Astragalus membranaceus</italic> and <italic>Yu Ping Feng</italic> were used in the 13 prevention programs (in Beijing, Tianjin, et al.) for “reinforcing vital <italic>qi</italic>”, a terminology used in TCM that is similar to boosting host defense capacity. <italic>Ophiopogon japonicas</italic> and <italic>Scrophularia ningpoensisand</italic> are TCM herbs which were most frequently used for “nourishing <italic>yin</italic>” in northern China, while <italic>Atractylodis Rhizoma, Agastache rugosa</italic> and other Chinese medicinal herbs with the property of “aromatic dehumidification” were commonly used in southern China (Table <xref rid="T6" ref-type="table">6</xref>).</p><p>According to the report of National Administration of Traditional Chinese Medicine, up to February 5th, 2020, 214 COVID-19 patients were treated with <italic>Qing Fei Pai Du Tang</italic> in Shanxi, Hebei, Heilongjiang and Shaanxi Provinces with overall effective rate ≥ 90%. Among them, the symptoms of majority of patients (≥60%) were markedly improved, while illness of others (30%) was stabilized <xref rid="B92" ref-type="bibr">92</xref>. After that, 701 COVID-19 patients were treated with <italic>Qing Fei Pai Du Tang</italic> in 10 provinces in China. The result showed that 130 patients (18.5%) were completely cured after treatment. The treatment also resulted in the disappearance of characteristic symptoms of COVID-19 such as fever and cough in 51 patients (7.27%). In addition, symptom improvement or stabilization were observed in 268 patients (38.2%), and in 212 patients (30.2%), respectively <xref rid="B87" ref-type="bibr">87</xref>. Yao, <italic>et al</italic>. and Lu, <italic>et al.</italic><xref rid="B93" ref-type="bibr">93</xref>, <xref rid="B94" ref-type="bibr">94</xref> retrospectively analyzed the clinical efficacy of <italic>Lian Hua Qing Wen Capsule</italic> in treatment of confirmed and suspected COVID-19 patients. The results indicated that this herbal product could markedly relieve major symptoms such as fever and cough and had the capacity to promote the recovery.</p><p>Some patients with mild illness in the early stage could suddenly progress to severe disease, and eventually died due to septic shock with multiple organ dysfunction syndrome (MODS), which was associated with cytokine storm <xref rid="B95" ref-type="bibr">95</xref>. There is compelling evidence that some TCM herbal products or its components have potent immunosuppressive effects, as shown by our own and other's studies <xref rid="B79" ref-type="bibr">79</xref>, <xref rid="B96" ref-type="bibr">96</xref>-<xref rid="B103" ref-type="bibr">103</xref>. For example, Wang, <italic>et al</italic>. <xref rid="B104" ref-type="bibr">104</xref> reported that <italic>Shen Fu Injection</italic> could inhibit the lung inflammation and decrease the levels of IL-1β, IL-6 and other cytokines. Chang, <italic>et al</italic>. <xref rid="B105" ref-type="bibr">105</xref> reported that <italic>Re Du Ning Injection</italic> could markedly reduce the levels of IL-1β, TNF-α, IL-8, IL-10, and some other cytokines of LPS-induced model of acute lung injury in rats. We recently reported that tetrandrine, a compound isolated from an anti-rheumatic Chinese herb, could potently inhibit proinflammatory Th1, Th2 and Th17 responses in LPS-challenged mice <xref rid="B106" ref-type="bibr">106</xref>. Therefore, TCM with the capacity to inhibit cytokine storm and its devastating consequences may be harnessed in the treatment of severe COVID-19 patients.</p><p>Currently, the laboratory study on the effect of TCM is apparently lagging behind the clinical application of TCM in the treatment of COVID-19 patients. Nevertheless, some scientists have started to examine the effect of TCM products or its components on SARS-CoV-2 in their laboratories. For example, an <italic>in vitro</italic> study showed that S<italic>huang Huang Lian Oral Liquid</italic> had the inhibitory effect on SARS-CoV-2 <xref rid="B78" ref-type="bibr">78</xref>. However, its clinical efficacy and safety for the treatment of COVID-19 patients has not been evaluated. We noticed that this TCM product was not recommended by HNC's Guideline <xref rid="B89" ref-type="bibr">89</xref>. Same as SARS-CoV, SARS-CoV-2 uses receptor ACE2 for the cellular entrance <xref rid="B8" ref-type="bibr">8</xref>. Theoretically, blockade of ACE2 can prevent the infection of SARS-CoV-2. Chen and Du thus performed the molecular docking study and they found that TCM-derived compounds, including as baicalin, scutellarin, hesperetin, glycyrrhizin and nicotianamine could interact with ACE2 <xref rid="B107" ref-type="bibr">107</xref>. Therefore, these compounds as well as herbs containing these ingredients may have the capacity to inhibit the infection of SARS-CoV-2. We anticipate more experiment studies showing anti-SARS-CoV-2 activity of TCM or its components will be published in the near future.</p></sec><sec><title>Closing remarks</title><p>TCM has accumulated thousand-of-year's experiences in the treatment of pandemic and endemic diseases. Providing complementary and alternative treatments are still urgently needed for the management of patients with SARS-CoV-2 infection, experiences in TCM is certainly worth learning. Fighting against current epidemics also provide an opportunity to test the true value of TCM in treating emerging contagious diseases. Randomized, double-blind and placebo-controlled studies is the best way to provide the most reliable evidence for a therapy, including TCM. It is encouraging that the controlled clinical studies to evaluate the efficacy of TCM in the treatment of SARS-CoV were conducted and reported. However, the most of these studies were found to be poorly designed and the results could lead to potential biases in evaluating the effectiveness of TCM treatment <xref rid="B13" ref-type="bibr">13</xref>. Hopefully, current clinical study to evaluate the effect of TCM on COVID-19 will use more strict protocols, concealment of allocation, and double-blinding, in order to ensure the compliance of international acceptable standards. Furthermore, standardized products of TCM, rather than self-prepared formulations, should be used in clinical study. Experiment study may be able to elucidate the mechanism underlying the therapeutic effect of TCM in the treatment of COVID-19. The further study of TCM may lead to the identification of novel anti human coronavirus compounds that may eventually prove to be useful in the treatment of SARS-CoV-2 or other emerging fatal viral diseases as conventional therapeutic agents.</p><p>The safety of TCM in the treatment of emerging coronavirus diseases was not included in the observation on SARS patients <xref rid="B13" ref-type="bibr">13</xref>. It was reported that some herbs used in TCM contain nephrotoxins and mutagens <xref rid="B108" ref-type="bibr">108</xref>, while the toxicological features of the most of Chinese herbal medicines remain to be fully understood <xref rid="B109" ref-type="bibr">109</xref>. Furthermore, herbs used in TCM can mimic, or magnify, or oppose the effect of conventional medicines <xref rid="B110" ref-type="bibr">110</xref>. Thus, the safety of TCM used in treatment of emerging coronavirus infections should be carefully evaluated. It is particularly important to avoid toxicity or interfere with the efficacy of conventional treatment caused by herb-drug interaction.</p></sec><sec sec-type="supplementary-material" id="SM0"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SM1"><caption><p>Supplementary figures and tables.</p></caption><media xlink:href="ijbsv16p1708s1.pdf"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material></sec></body><back><ack><p>This project has been funded by Macau Science and Technology Development Fund (FDCT) research grant 201/2017/A3 and 0056/2019/AFJ and University of Macau research grant MYRG2017-00120- ICMS and MYRG2019-00169-ICMS.</p></ack><ref-list><ref id="B1"><label>1</label><element-citation publication-type="other"><name><surname>Gralinski</surname><given-names>LE</given-names></name><name><surname>Menachery</surname><given-names>VD</given-names></name><article-title>Return of the Coronavirus: 2019-nCoV</article-title><source>Viruses</source><year>2020</year><comment>12</comment></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="other"><name><surname>Burki</surname><given-names>TK</given-names></name><article-title>Coronavirus in China</article-title><source>Lancet Respir Med</source><year>2020</year></element-citation></ref><ref id="B3"><label>3</label><element-citation publication-type="other"><collab>World Health Organization</collab><article-title>WHO Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020</article-title><source>https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020</source><year>2020</year></element-citation></ref><ref id="B4"><label>4</label><element-citation publication-type="other"><name><surname>Guan</surname><given-names>WJ</given-names></name><name><surname>Ni</surname><given-names>ZY</given-names></name><name><surname>Hu</surname><given-names>Y</given-names></name><name><surname>Liang</surname><given-names>WH</given-names></name><name><surname>Ou</surname><given-names>CQ</given-names></name><name><surname>He</surname><given-names>JX</given-names></name><etal></etal><article-title>Clinical characteristics of 2019 novel coronavirus infection in China</article-title><source>medRxiv. 2020</source><year>2020</year><comment>02.06.20020974</comment></element-citation></ref><ref id="B5"><label>5</label><element-citation publication-type="journal"><name><surname>Huang</surname><given-names>C</given-names></name><name><surname>Wang</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><name><surname>Ren</surname><given-names>L</given-names></name><name><surname>Zhao</surname><given-names>J</given-names></name><name><surname>Hu</surname><given-names>Y</given-names></name><etal></etal><article-title>Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China</article-title><source>Lancet</source><year>2020</year><volume>395</volume><issue>10223</issue><fpage>497</fpage><lpage>506</lpage><pub-id pub-id-type="pmid">31986264</pub-id></element-citation></ref><ref id="B6"><label>6</label><element-citation publication-type="other"><collab>World Health Organization</collab><article-title>Situation Report-29</article-title><source>https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200218-sitrep-29-covid-19.pdf?sfvrsn=6262de9e_2</source><year>2020</year></element-citation></ref><ref id="B7"><label>7</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>N</given-names></name><name><surname>Zhou</surname><given-names>M</given-names></name><name><surname>Dong</surname><given-names>X</given-names></name><name><surname>Qu</surname><given-names>J</given-names></name><name><surname>Gong</surname><given-names>F</given-names></name><name><surname>Han</surname><given-names>Y</given-names></name><etal></etal><article-title>Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study</article-title><source>Lancet</source><year>2020</year><volume>395</volume><issue>10223</issue><fpage>507</fpage><lpage>513</lpage><pub-id pub-id-type="pmid">32007143</pub-id></element-citation></ref><ref id="B8"><label>8</label><element-citation publication-type="other"><name><surname>Zhou</surname><given-names>P</given-names></name><name><surname>Yang</surname><given-names>XL</given-names></name><name><surname>Wang</surname><given-names>XG</given-names></name><name><surname>Hu</surname><given-names>B</given-names></name><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Zhang</surname><given-names>W</given-names></name><etal></etal><article-title>A pneumonia outbreak associated with a new coronavirus of probable bat origin</article-title><source>Nature</source><year>2020</year></element-citation></ref><ref id="B9"><label>9</label><element-citation publication-type="other"><name><surname>Wu</surname><given-names>A</given-names></name><name><surname>Peng</surname><given-names>Y</given-names></name><name><surname>Huang</surname><given-names>B</given-names></name><name><surname>Ding</surname><given-names>X</given-names></name><name><surname>Wang</surname><given-names>X</given-names></name><name><surname>Niu</surname><given-names>P</given-names></name><etal></etal><article-title>Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China</article-title><source>Cell Host Microbe</source><year>2020</year></element-citation></ref><ref id="B10"><label>10</label><element-citation publication-type="journal"><name><surname>Zumla</surname><given-names>A</given-names></name><name><surname>Chan</surname><given-names>JF</given-names></name><name><surname>Azhar</surname><given-names>EI</given-names></name><name><surname>Hui</surname><given-names>DS</given-names></name><name><surname>Yuen</surname><given-names>KY</given-names></name><article-title>Coronaviruses - drug discovery and therapeutic options</article-title><source>Nat Rev Drug Discov</source><year>2016</year><volume>15</volume><fpage>327</fpage><lpage>47</lpage><pub-id pub-id-type="pmid">26868298</pub-id></element-citation></ref><ref id="B11"><label>11</label><element-citation publication-type="other"><name><surname>Xie</surname><given-names>X</given-names></name><name><surname>Zhong</surname><given-names>Z</given-names></name><name><surname>Zhao</surname><given-names>W</given-names></name><name><surname>Zheng</surname><given-names>C</given-names></name><name><surname>Wang</surname><given-names>F</given-names></name><name><surname>Liu</surname><given-names>J</given-names></name><article-title>Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing</article-title><source>Radiology. 2020: 200343</source></element-citation></ref><ref id="B12"><label>12</label><element-citation publication-type="other"><name><surname>Li</surname><given-names>G</given-names></name><name><surname>Clercq</surname><given-names>ED</given-names></name><article-title>Therapeutic options for the 2019 novel coronavirus (2019-nCoV)</article-title><source>Nat Rev Drug Discov</source><year>2020</year></element-citation></ref><ref id="B13"><label>13</label><element-citation publication-type="journal"><name><surname>Liu</surname><given-names>J</given-names></name><name><surname>Manheimer</surname><given-names>E</given-names></name><name><surname>Shi</surname><given-names>Y</given-names></name><name><surname>Gluud</surname><given-names>C</given-names></name><article-title>Chinese herbal medicine for severe acute respiratory syndrome: a systematic review and meta-analysis</article-title><source>J Altern Complement Med</source><year>2004</year><volume>10</volume><fpage>1041</fpage><lpage>51</lpage><pub-id pub-id-type="pmid">15674000</pub-id></element-citation></ref><ref id="B14"><label>14</label><element-citation publication-type="journal"><name><surname>Li</surname><given-names>T</given-names></name><name><surname>Peng</surname><given-names>T</given-names></name><article-title>Traditional Chinese herbal medicine as a source of molecules with antiviral activity</article-title><source>Antiviral Res</source><year>2013</year><volume>97</volume><fpage>1</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">23153834</pub-id></element-citation></ref><ref id="B15"><label>15</label><element-citation publication-type="journal"><name><surname>Leung</surname><given-names>PC</given-names></name><article-title>The efficacy of Chinese medicine for SARS: a review of Chinese publications after the crisis</article-title><source>Am J Chin Med</source><year>2007</year><volume>35</volume><fpage>575</fpage><lpage>81</lpage><pub-id pub-id-type="pmid">17708624</pub-id></element-citation></ref><ref id="B16"><label>16</label><element-citation publication-type="journal"><name><surname>Jin</surname><given-names>YH</given-names></name><name><surname>Cai</surname><given-names>L</given-names></name><name><surname>Cheng</surname><given-names>ZS</given-names></name><name><surname>Cheng</surname><given-names>H</given-names></name><name><surname>Deng</surname><given-names>T</given-names></name><name><surname>Fan</surname><given-names>YP</given-names></name><etal></etal><article-title>A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)</article-title><source>Mil Med Res</source><year>2020</year><volume>7</volume><fpage>4</fpage><pub-id pub-id-type="pmid">32029004</pub-id></element-citation></ref><ref id="B17"><label>17</label><element-citation publication-type="journal"><name><surname>Habibzadeh</surname><given-names>P</given-names></name><name><surname>Stoneman</surname><given-names>EK</given-names></name><article-title>The Novel Coronavirus: A Bird's Eye View</article-title><source>Int J Occup Environ Med</source><year>2020</year><volume>11</volume><fpage>65</fpage><lpage>71</lpage><pub-id pub-id-type="pmid">32020915</pub-id></element-citation></ref><ref id="B18"><label>18</label><element-citation publication-type="journal"><name><surname>Jordan</surname><given-names>PC</given-names></name><name><surname>Stevens</surname><given-names>SK</given-names></name><name><surname>Deval</surname><given-names>J</given-names></name><article-title>Nucleosides for the treatment of respiratory RNA virus infections</article-title><source>Antivir Chem Chemother</source><year>2018</year><volume>26</volume><fpage>2040206618764483</fpage><pub-id pub-id-type="pmid">29562753</pub-id></element-citation></ref><ref id="B19"><label>19</label><element-citation publication-type="journal"><name><surname>De Clercq</surname><given-names>E</given-names></name><article-title>New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections</article-title><source>Chem Asian J</source><year>2019</year><volume>14</volume><fpage>3962</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">31389664</pub-id></element-citation></ref><ref id="B20"><label>20</label><element-citation publication-type="other"><name><surname>Wang</surname><given-names>M</given-names></name><name><surname>Cao</surname><given-names>R</given-names></name><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Yang</surname><given-names>X</given-names></name><name><surname>Liu</surname><given-names>J</given-names></name><name><surname>Xu</surname><given-names>M</given-names></name><etal></etal><article-title>Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro</article-title><source>Cell Res</source><year>2020</year></element-citation></ref><ref id="B21"><label>21</label><element-citation publication-type="other"><name><surname>Sheahan</surname><given-names>TP</given-names></name><name><surname>Sims</surname><given-names>AC</given-names></name><name><surname>Graham</surname><given-names>RL</given-names></name><name><surname>Menachery</surname><given-names>VD</given-names></name><name><surname>Gralinski</surname><given-names>LE</given-names></name><name><surname>Case</surname><given-names>JB</given-names></name><etal></etal><article-title>Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses</article-title><source>Sci Transl Med</source><year>2017</year><comment>9</comment></element-citation></ref><ref id="B22"><label>22</label><element-citation publication-type="other"><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Liu</surname><given-names>Y</given-names></name><article-title>Potential Interventions for Novel Coronavirus in China: A Systemic Review</article-title><source>J Med Virol</source><year>2020</year></element-citation></ref><ref id="B23"><label>23</label><element-citation publication-type="other"><name><surname>Holshue</surname><given-names>ML</given-names></name><name><surname>DeBolt</surname><given-names>C</given-names></name><name><surname>Lindquist</surname><given-names>S</given-names></name><name><surname>Lofy</surname><given-names>KH</given-names></name><name><surname>Wiesman</surname><given-names>J</given-names></name><name><surname>Bruce</surname><given-names>H</given-names></name><etal></etal><article-title>First Case of 2019 Novel Coronavirus in the United States</article-title><source>N Engl J Med</source><year>2020</year></element-citation></ref><ref id="B24"><label>24</label><element-citation publication-type="other"><name><surname>Lai</surname><given-names>CC</given-names></name><name><surname>Shih</surname><given-names>TP</given-names></name><name><surname>Ko</surname><given-names>WC</given-names></name><name><surname>Tang</surname><given-names>HJ</given-names></name><name><surname>Hsueh</surname><given-names>PR</given-names></name><article-title>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges</article-title><source>Int J Antimicrob Agents. 2020: 105924</source></element-citation></ref><ref id="B25"><label>25</label><element-citation publication-type="journal"><name><surname>Savarino</surname><given-names>A</given-names></name><name><surname>Di Trani</surname><given-names>L</given-names></name><name><surname>Donatelli</surname><given-names>I</given-names></name><name><surname>Cauda</surname><given-names>R</given-names></name><name><surname>Cassone</surname><given-names>A</given-names></name><article-title>New insights into the antiviral effects of chloroquine</article-title><source>Lancet Infect Dis</source><year>2006</year><volume>6</volume><fpage>67</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">16439323</pub-id></element-citation></ref><ref id="B26"><label>26</label><element-citation publication-type="journal"><name><surname>Yan</surname><given-names>Y</given-names></name><name><surname>Zou</surname><given-names>Z</given-names></name><name><surname>Sun</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><name><surname>Xu</surname><given-names>KF</given-names></name><name><surname>Wei</surname><given-names>Y</given-names></name><etal></etal><article-title>Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model</article-title><source>Cell Res</source><year>2013</year><volume>23</volume><fpage>300</fpage><lpage>2</lpage><pub-id pub-id-type="pmid">23208422</pub-id></element-citation></ref><ref id="B27"><label>27</label><element-citation publication-type="journal"><name><surname>Wong</surname><given-names>CK</given-names></name><name><surname>Lam</surname><given-names>CW</given-names></name><name><surname>Wu</surname><given-names>AK</given-names></name><name><surname>Ip</surname><given-names>WK</given-names></name><name><surname>Lee</surname><given-names>NL</given-names></name><name><surname>Chan</surname><given-names>IH</given-names></name><etal></etal><article-title>Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome</article-title><source>Clin Exp Immuno</source><year>2004</year><volume>136</volume><fpage>95</fpage><lpage>103</lpage></element-citation></ref><ref id="B28"><label>28</label><element-citation publication-type="journal"><name><surname>He</surname><given-names>L</given-names></name><name><surname>Ding</surname><given-names>Y</given-names></name><name><surname>Zhang</surname><given-names>Q</given-names></name><name><surname>Che</surname><given-names>X</given-names></name><name><surname>He</surname><given-names>Y</given-names></name><name><surname>Shen</surname><given-names>H</given-names></name><etal></etal><article-title>Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS</article-title><source>J Pathol</source><year>2006</year><volume>210</volume><fpage>288</fpage><lpage>97</lpage><pub-id pub-id-type="pmid">17031779</pub-id></element-citation></ref><ref id="B29"><label>29</label><element-citation publication-type="journal"><name><surname>Faure</surname><given-names>E</given-names></name><name><surname>Poissy</surname><given-names>J</given-names></name><name><surname>Goffard</surname><given-names>A</given-names></name><name><surname>Fournier</surname><given-names>C</given-names></name><name><surname>Kipnis</surname><given-names>E</given-names></name><name><surname>Titecat</surname><given-names>M</given-names></name><etal></etal><article-title>Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside?</article-title><source>PLoS One</source><year>2014</year><volume>9</volume><fpage>e88716</fpage><pub-id pub-id-type="pmid">24551142</pub-id></element-citation></ref><ref id="B30"><label>30</label><element-citation publication-type="journal"><name><surname>Falzarano</surname><given-names>D</given-names></name><name><surname>de Wit</surname><given-names>E</given-names></name><name><surname>Rasmussen</surname><given-names>AL</given-names></name><name><surname>Feldmann</surname><given-names>F</given-names></name><name><surname>Okumura</surname><given-names>A</given-names></name><name><surname>Scott</surname><given-names>DP</given-names></name><etal></etal><article-title>Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques</article-title><source>Nat Med</source><year>2013</year><volume>19</volume><fpage>1313</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">24013700</pub-id></element-citation></ref><ref id="B31"><label>31</label><element-citation publication-type="journal"><name><surname>Stockman</surname><given-names>LJ</given-names></name><name><surname>Bellamy</surname><given-names>R</given-names></name><name><surname>Garner</surname><given-names>P</given-names></name><article-title>SARS: systematic review of treatment effects</article-title><source>PLoS Med</source><year>2006</year><volume>3</volume><fpage>e343</fpage><pub-id pub-id-type="pmid">16968120</pub-id></element-citation></ref><ref id="B32"><label>32</label><element-citation publication-type="journal"><name><surname>Lansbury</surname><given-names>L</given-names></name><name><surname>Rodrigo</surname><given-names>C</given-names></name><name><surname>Leonardi-Bee</surname><given-names>J</given-names></name><name><surname>Nguyen-Van-Tam</surname><given-names>J</given-names></name><name><surname>Lim</surname><given-names>WS</given-names></name><article-title>Corticosteroids as adjunctive therapy in the treatment of influenza</article-title><source>Cochrane Database Syst Rev</source><year>2019</year><volume>2</volume><fpage>Cd010406</fpage><pub-id pub-id-type="pmid">30798570</pub-id></element-citation></ref><ref id="B33"><label>33</label><element-citation publication-type="journal"><name><surname>Arabi</surname><given-names>YM</given-names></name><name><surname>Mandourah</surname><given-names>Y</given-names></name><name><surname>Al-Hameed</surname><given-names>F</given-names></name><name><surname>Sindi</surname><given-names>AA</given-names></name><name><surname>Almekhlafi</surname><given-names>GA</given-names></name><name><surname>Hussein</surname><given-names>MA</given-names></name><etal></etal><article-title>Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome</article-title><source>Am J Respir Crit Care Med</source><year>2018</year><volume>197</volume><fpage>757</fpage><lpage>67</lpage><pub-id pub-id-type="pmid">29161116</pub-id></element-citation></ref><ref id="B34"><label>34</label><element-citation publication-type="other"><name><surname>Russell</surname><given-names>CD</given-names></name><name><surname>Millar</surname><given-names>JE</given-names></name><name><surname>Baillie</surname><given-names>JK</given-names></name><article-title>Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury</article-title><source>Lancet</source><year>2020</year></element-citation></ref><ref id="B35"><label>35</label><mixed-citation publication-type="other"><comment>World Health Organization. https://www.who.int/internal-publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected. 2020</comment></mixed-citation></ref><ref id="B36"><label>36</label><element-citation publication-type="journal"><name><surname>Hung</surname><given-names>IFN</given-names></name><name><surname>To</surname><given-names>KKW</given-names></name><name><surname>Lee</surname><given-names>CK</given-names></name><name><surname>Lee</surname><given-names>KL</given-names></name><name><surname>Yan</surname><given-names>WW</given-names></name><name><surname>Chan</surname><given-names>K</given-names></name><etal></etal><article-title>Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection</article-title><source>Chest</source><year>2013</year><volume>144</volume><fpage>464</fpage><lpage>73</lpage><pub-id pub-id-type="pmid">23450336</pub-id></element-citation></ref><ref id="B37"><label>37</label><element-citation publication-type="other"><name><surname>Luo</surname><given-names>H</given-names></name><name><surname>Tang</surname><given-names>QL</given-names></name><name><surname>Shang</surname><given-names>YX</given-names></name><name><surname>Liang</surname><given-names>SB</given-names></name><name><surname>Yang</surname><given-names>M</given-names></name><name><surname>Robinson</surname><given-names>N</given-names></name><etal></etal><article-title>Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs</article-title><source>Chin J Integr Med</source><year>2020</year></element-citation></ref><ref id="B38"><label>38</label><element-citation publication-type="journal"><name><surname>Tong</surname><given-names>X</given-names></name><name><surname>Li</surname><given-names>A</given-names></name><name><surname>Zhang</surname><given-names>Z</given-names></name><name><surname>Duan</surname><given-names>J</given-names></name><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Hua</surname><given-names>C</given-names></name><etal></etal><article-title>TCM treatment of infectious atypical pneumonia-a report of 16 cases</article-title><source>J Tradit Chin Med</source><year>2004</year><volume>24</volume><fpage>266</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">15688692</pub-id></element-citation></ref><ref id="B39"><label>39</label><element-citation publication-type="journal"><name><surname>Liu</surname><given-names>X</given-names></name><name><surname>Zhang</surname><given-names>M</given-names></name><name><surname>He</surname><given-names>L</given-names></name><name><surname>Li</surname><given-names>Y</given-names></name><article-title>Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS)</article-title><source>Cochrane Database Syst Rev</source><year>2012</year><volume>10</volume><fpage>Cd004882</fpage><pub-id pub-id-type="pmid">23076910</pub-id></element-citation></ref><ref id="B40"><label>40</label><element-citation publication-type="journal"><name><surname>Zhang</surname><given-names>MM</given-names></name><name><surname>Liu</surname><given-names>XM</given-names></name><name><surname>He</surname><given-names>L</given-names></name><article-title>Effect of integrated traditional Chinese and Western medicine on SARS: a review of clinical evidence</article-title><source>World J Gastroenterol</source><year>2004</year><volume>10</volume><fpage>3500</fpage><lpage>5</lpage><pub-id pub-id-type="pmid">15526373</pub-id></element-citation></ref><ref id="B41"><label>41</label><element-citation publication-type="journal"><name><surname>Zhong</surname><given-names>N</given-names></name><name><surname>May</surname><given-names>RM</given-names></name><name><surname>McLean</surname><given-names>AR</given-names></name><name><surname>Pattison</surname><given-names>J</given-names></name><name><surname>Weiss</surname><given-names>RA</given-names></name><article-title>Management and prevention of SARS in China</article-title><source>Philos Trans R Soc Lond B Biol Sci</source><year>2004</year><volume>359</volume><fpage>1115</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">15306397</pub-id></element-citation></ref><ref id="B42"><label>42</label><element-citation publication-type="journal"><name><surname>JSM</surname><given-names>P</given-names></name><name><surname>D</surname><given-names>P</given-names></name><name><surname>Yuen KY</surname><given-names>ea</given-names></name><article-title>The Severe Acute Respiratory Syndrome</article-title><source>New Engl J Med</source><year>2003</year><volume>249</volume><fpage>2431</fpage><lpage>41</lpage></element-citation></ref><ref id="B43"><label>43</label><element-citation publication-type="journal"><name><surname>Jr</surname><given-names>TMF</given-names></name><name><surname>Tsang</surname><given-names>KWT</given-names></name><article-title>Severe Acute Respiratory Syndrome</article-title><source>Nat Med</source><year>2005</year><volume>4</volume><fpage>95</fpage><lpage>106</lpage></element-citation></ref><ref id="B44"><label>44</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>Z</given-names></name><name><surname>Nakamura</surname><given-names>T</given-names></name><article-title>Statistical evidence for the usefulness of Chinese medicine in the treatment of SARS</article-title><source>Phytotherapy research: PTR</source><year>2004</year><volume>18</volume><fpage>592</fpage><lpage>4</lpage><pub-id pub-id-type="pmid">15305324</pub-id></element-citation></ref><ref id="B45"><label>45</label><element-citation publication-type="journal"><collab>T.F</collab><article-title>Lau, Leung PC, Wong ELY, Fong C, Cheng KF, Zhang SC, et al. Using Herbal Medicine as a Means of Prevention Experience During the SARS Crisis</article-title><source>Am J Chin Med</source><year>2005</year><volume>33</volume><fpage>345</fpage><lpage>56</lpage><pub-id pub-id-type="pmid">16047553</pub-id></element-citation></ref><ref id="B46"><label>46</label><element-citation publication-type="journal"><name><surname>Poon</surname><given-names>PM</given-names></name><name><surname>Wong</surname><given-names>CK</given-names></name><name><surname>Fung</surname><given-names>KP</given-names></name><name><surname>Fong</surname><given-names>CY</given-names></name><name><surname>Wong</surname><given-names>EL</given-names></name><name><surname>Lau</surname><given-names>JT</given-names></name><etal></etal><article-title>Immunomodulatory effects of a traditional Chinese medicine with potential antiviral activity: a self-control study</article-title><source>Am J Chin Med</source><year>2006</year><volume>34</volume><fpage>13</fpage><lpage>21</lpage><pub-id pub-id-type="pmid">16437735</pub-id></element-citation></ref><ref id="B47"><label>47</label><element-citation publication-type="journal"><name><surname>Hsu</surname><given-names>CH</given-names></name><name><surname>Hwang</surname><given-names>KC</given-names></name><name><surname>Chao</surname><given-names>CL</given-names></name><name><surname>Chang</surname><given-names>SG</given-names></name><name><surname>Ho</surname><given-names>MS</given-names></name><name><surname>Chou</surname><given-names>P</given-names></name><article-title>Can herbal medicine assist against avian flu? Learning from the experience of using supplementary treatment with Chinese medicine on SARS or SARS-like infectious disease in 2003</article-title><source>J Altern Complement Med</source><year>2006</year><volume>12</volume><fpage>505</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">16884338</pub-id></element-citation></ref><ref id="B48"><label>48</label><element-citation publication-type="journal"><name><surname>Cinatl</surname><given-names>J</given-names></name><name><surname>Morgenstern</surname><given-names>B</given-names></name><name><surname>Bauer</surname><given-names>G</given-names></name><name><surname>Chandra</surname><given-names>P</given-names></name><name><surname>Rabenau</surname><given-names>H</given-names></name><name><surname>Doerr</surname><given-names>HW</given-names></name><article-title>Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus</article-title><source>The Lancet</source><year>2003</year><volume>361</volume><fpage>2045</fpage><lpage>6</lpage></element-citation></ref><ref id="B49"><label>49</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>F</given-names></name><name><surname>Chan</surname><given-names>KH</given-names></name><name><surname>Jiang</surname><given-names>Y</given-names></name><name><surname>Kao</surname><given-names>RY</given-names></name><name><surname>Lu</surname><given-names>HT</given-names></name><name><surname>Fan</surname><given-names>KW</given-names></name><etal></etal><article-title>In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds</article-title><source>J Clin Virol</source><year>2004</year><volume>31</volume><fpage>69</fpage><lpage>75</lpage><pub-id pub-id-type="pmid">15288617</pub-id></element-citation></ref><ref id="B50"><label>50</label><element-citation publication-type="journal"><name><surname>Wang</surname><given-names>SQ</given-names></name><name><surname>Du</surname><given-names>QS</given-names></name><name><surname>Zhao</surname><given-names>K</given-names></name><name><surname>Li</surname><given-names>AX</given-names></name><name><surname>Wei</surname><given-names>DQ</given-names></name><name><surname>Chou</surname><given-names>KC</given-names></name><article-title>Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy</article-title><source>Amino Acids</source><year>2007</year><volume>33</volume><fpage>129</fpage><lpage>35</lpage><pub-id pub-id-type="pmid">16998715</pub-id></element-citation></ref><ref id="B51"><label>51</label><element-citation publication-type="journal"><name><surname>Wu</surname><given-names>T</given-names></name><name><surname>Yang</surname><given-names>X</given-names></name><name><surname>Zeng</surname><given-names>X</given-names></name><name><surname>Poole</surname><given-names>P</given-names></name><article-title>Traditional Chinese medicine in the treatment of acute respiratory tract infections</article-title><source>Resp Med</source><year>2008</year><volume>102</volume><fpage>1093</fpage><lpage>8</lpage></element-citation></ref><ref id="B52"><label>52</label><element-citation publication-type="journal"><name><surname>Cragg</surname><given-names>GM</given-names></name><name><surname>Newman</surname><given-names>DJ</given-names></name><article-title>Natural products: a continuing source of novel drug leads</article-title><source>Biochimica et biophysica acta</source><year>2013</year><volume>1830</volume><fpage>3670</fpage><lpage>95</lpage><pub-id pub-id-type="pmid">23428572</pub-id></element-citation></ref><ref id="B53"><label>53</label><element-citation publication-type="other"><name><surname>Luo</surname><given-names>W</given-names></name><name><surname>Su</surname><given-names>X</given-names></name><name><surname>Gong</surname><given-names>S</given-names></name><name><surname>Qin</surname><given-names>Y</given-names></name><name><surname>Liu</surname><given-names>W</given-names></name><name><surname>Li</surname><given-names>J</given-names></name><etal></etal><article-title>Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L</article-title><source>extracts. BioScience Trends</source><year>2009</year><comment>3</comment></element-citation></ref><ref id="B54"><label>54</label><element-citation publication-type="journal"><name><surname>Fung</surname><given-names>KP</given-names></name><name><surname>Leung</surname><given-names>PC</given-names></name><name><surname>Tsui</surname><given-names>KW</given-names></name><name><surname>Wan</surname><given-names>CC</given-names></name><name><surname>Wong</surname><given-names>KB</given-names></name><name><surname>Waye</surname><given-names>MY</given-names></name><etal></etal><article-title>Immunomodulatory activities of the herbal formula Kwan Du Bu Fei Dang in healthy subjects: a randomised, double-blind, placebo-controlled study</article-title><source>Hong Kong Med J</source><year>2011</year><volume>17</volume><issue>Suppl 2</issue><fpage>41</fpage><lpage>3</lpage></element-citation></ref><ref id="B55"><label>55</label><element-citation publication-type="journal"><name><surname>Lau</surname><given-names>KM</given-names></name><name><surname>Lee</surname><given-names>KM</given-names></name><name><surname>Koon</surname><given-names>CM</given-names></name><name><surname>Cheung</surname><given-names>CS</given-names></name><name><surname>Lau</surname><given-names>CP</given-names></name><name><surname>Ho</surname><given-names>HM</given-names></name><etal></etal><article-title>Immunomodulatory and anti-SARS activities of Houttuynia cordata</article-title><source>J Ethnopharmacol</source><year>2008</year><volume>118</volume><fpage>79</fpage><lpage>85</lpage><pub-id pub-id-type="pmid">18479853</pub-id></element-citation></ref><ref id="B56"><label>56</label><element-citation publication-type="journal"><name><surname>Gong</surname><given-names>SJ</given-names></name><name><surname>Su</surname><given-names>XJ</given-names></name><name><surname>Yu</surname><given-names>HP</given-names></name><name><surname>Li</surname><given-names>J</given-names></name><name><surname>Qin</surname><given-names>YJ</given-names></name><name><surname>Xu</surname><given-names>Q</given-names></name><etal></etal><article-title>A study on anti-SARS-CoV 3CL protein of flavonoids from litchi chinensis sonn core</article-title><source>Chinese Pharmacological Bulletin</source><year>2008</year><volume>24</volume><fpage>699</fpage><lpage>700</lpage></element-citation></ref><ref id="B57"><label>57</label><element-citation publication-type="journal"><name><surname>Lin</surname><given-names>CW</given-names></name><name><surname>Tsai</surname><given-names>FJ</given-names></name><name><surname>Tsai</surname><given-names>CH</given-names></name><name><surname>Lai</surname><given-names>CC</given-names></name><name><surname>Wan</surname><given-names>L</given-names></name><name><surname>Ho</surname><given-names>TY</given-names></name><etal></etal><article-title>Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds</article-title><source>Antiviral Res</source><year>2005</year><volume>68</volume><fpage>36</fpage><lpage>42</lpage><pub-id pub-id-type="pmid">16115693</pub-id></element-citation></ref><ref id="B58"><label>58</label><element-citation publication-type="journal"><name><surname>Nguyen</surname><given-names>TTH</given-names></name><name><surname>Woo</surname><given-names>HJ</given-names></name><name><surname>Kang</surname><given-names>HK</given-names></name><name><surname>Nguyen</surname><given-names>VD</given-names></name><name><surname>Kim</surname><given-names>YM</given-names></name><name><surname>Kim</surname><given-names>DW</given-names></name><etal></etal><article-title>Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris</article-title><source>Biotechnol Lett</source><year>2012</year><volume>34</volume><fpage>831</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">22350287</pub-id></element-citation></ref><ref id="B59"><label>59</label><element-citation publication-type="journal"><name><surname>Jo</surname><given-names>S</given-names></name><name><surname>Kim</surname><given-names>S</given-names></name><name><surname>Shin</surname><given-names>DH</given-names></name><name><surname>Kim</surname><given-names>M-S</given-names></name><article-title>Inhibition of SARS-CoV 3CL protease by flavonoids</article-title><source>J Enzyme Inhib Med Chem</source><year>2020</year><volume>35</volume><fpage>145</fpage><lpage>51</lpage><pub-id pub-id-type="pmid">31724441</pub-id></element-citation></ref><ref id="B60"><label>60</label><element-citation publication-type="other"><name><surname>Jo</surname><given-names>S</given-names></name><name><surname>Kim</surname><given-names>H</given-names></name><name><surname>Kim</surname><given-names>S</given-names></name><name><surname>Shin</surname><given-names>DH</given-names></name><name><surname>Kim</surname><given-names>MS</given-names></name><article-title>Characteristics of flavonoids as potent MERS-CoV 3C-like protease inhibitors</article-title><source>Chem Biol Drug Des</source><year>2019</year></element-citation></ref><ref id="B61"><label>61</label><element-citation publication-type="journal"><name><surname>Yu</surname><given-names>MS</given-names></name><name><surname>Lee</surname><given-names>J</given-names></name><name><surname>Lee</surname><given-names>JM</given-names></name><name><surname>Kim</surname><given-names>Y</given-names></name><name><surname>Chin</surname><given-names>YW</given-names></name><name><surname>Jee</surname><given-names>JG</given-names></name><etal></etal><article-title>Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13</article-title><source>Bioorg Med Chem Lett</source><year>2012</year><volume>22</volume><fpage>4049</fpage><lpage>54</lpage><pub-id pub-id-type="pmid">22578462</pub-id></element-citation></ref><ref id="B62"><label>62</label><element-citation publication-type="journal"><name><surname>Wu</surname><given-names>CY</given-names></name><name><surname>Jan</surname><given-names>JT</given-names></name><name><surname>Ma</surname><given-names>SH</given-names></name><name><surname>Kuo</surname><given-names>CJ</given-names></name><name><surname>Juan</surname><given-names>HF</given-names></name><name><surname>Cheng</surname><given-names>YSE</given-names></name><etal></etal><article-title>Small molecules targeting severe acute respiratory syndrome human coronavirus</article-title><source>Proc Natl Acad Sci U S A</source><year>2004</year><volume>101</volume><fpage>10012</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">15226499</pub-id></element-citation></ref><ref id="B63"><label>63</label><element-citation publication-type="other"><name><surname>Kuhn</surname><given-names>JH</given-names></name><name><surname>Radoshitzky</surname><given-names>SR</given-names></name><name><surname>Li</surname><given-names>W</given-names></name><name><surname>Wong</surname><given-names>SK</given-names></name><name><surname>Choe</surname><given-names>H</given-names></name><name><surname>Farzan</surname><given-names>M</given-names></name><article-title>The SARS Coronavirus receptor ACE 2 A potential target for antiviral therapy</article-title><source>In: Holzenburg A, Bogner E, editors. New Concepts of Antiviral Therapy. Boston, MA: Springer US</source><year>2006</year><comment>p. 397-418</comment></element-citation></ref><ref id="B64"><label>64</label><element-citation publication-type="other"><name><surname>Letko</surname><given-names>M</given-names></name><name><surname>Munster</surname><given-names>V</given-names></name><article-title>Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV</article-title><source>bioRxiv. 2020</source><year>2020</year><comment>01.22.915660</comment></element-citation></ref><ref id="B65"><label>65</label><element-citation publication-type="journal"><name><surname>Lin</surname><given-names>HX</given-names></name><name><surname>Feng</surname><given-names>Y</given-names></name><name><surname>Wong</surname><given-names>G</given-names></name><name><surname>Wang</surname><given-names>L</given-names></name><name><surname>Li</surname><given-names>B</given-names></name><name><surname>Zhao</surname><given-names>X</given-names></name><etal></etal><article-title>Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor interaction</article-title><source>J Gen Virol</source><year>2008</year><volume>89</volume><fpage>1015</fpage><lpage>24</lpage><pub-id pub-id-type="pmid">18343844</pub-id></element-citation></ref><ref id="B66"><label>66</label><element-citation publication-type="other"><name><surname>Xu</surname><given-names>XT</given-names></name><name><surname>Chen</surname><given-names>P</given-names></name><name><surname>Wang</surname><given-names>JF</given-names></name><name><surname>Feng</surname><given-names>JN</given-names></name><name><surname>Zhou</surname><given-names>H</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><etal></etal><article-title>Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission</article-title><source>Sci China Life Sci</source><year>2020</year></element-citation></ref><ref id="B67"><label>67</label><element-citation publication-type="journal"><name><surname>Ho</surname><given-names>T</given-names></name><name><surname>Wu</surname><given-names>S</given-names></name><name><surname>Chen</surname><given-names>J</given-names></name><name><surname>Li</surname><given-names>C</given-names></name><name><surname>Hsiang</surname><given-names>C</given-names></name><article-title>Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction</article-title><source>Antiviral Res</source><year>2007</year><volume>74</volume><fpage>92</fpage><lpage>101</lpage><pub-id pub-id-type="pmid">16730806</pub-id></element-citation></ref><ref id="B68"><label>68</label><element-citation publication-type="journal"><name><surname>Deng</surname><given-names>YF</given-names></name><name><surname>Aluko</surname><given-names>RE</given-names></name><name><surname>Jin</surname><given-names>Q</given-names></name><name><surname>Zhang</surname><given-names>Y</given-names></name><name><surname>Yuan</surname><given-names>LJ</given-names></name><article-title>Inhibitory activities of baicalin against renin and angiotensin-converting enzyme</article-title><source>Pharm Biol</source><year>2012</year><volume>50</volume><fpage>401</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">22136493</pub-id></element-citation></ref><ref id="B69"><label>69</label><element-citation publication-type="journal"><name><surname>Takahashi</surname><given-names>S</given-names></name><name><surname>Yoshiya</surname><given-names>T</given-names></name><name><surname>Yoshizawa-Kumagaye</surname><given-names>K</given-names></name><name><surname>Sugiyama</surname><given-names>T</given-names></name><article-title>Nicotianamine is a novel angiotensin-converting enzyme 2 inhibitor in soybean</article-title><source>Biomed Res</source><year>2015</year><volume>36</volume><fpage>219</fpage><lpage>24</lpage><pub-id pub-id-type="pmid">26106051</pub-id></element-citation></ref><ref id="B70"><label>70</label><element-citation publication-type="journal"><name><surname>Wang</surname><given-names>W</given-names></name><name><surname>Ma</surname><given-names>X</given-names></name><name><surname>Han</surname><given-names>J</given-names></name><name><surname>Zhou</surname><given-names>M</given-names></name><name><surname>Ren</surname><given-names>H</given-names></name><name><surname>Pan</surname><given-names>Q</given-names></name><etal></etal><article-title>Neuroprotective Effect of Scutellarin on Ischemic Cerebral Injury by Down-Regulating the Expression of Angiotensin-Converting Enzyme and AT1 Receptor</article-title><source>PLoS One</source><year>2016</year><volume>11</volume><fpage>e0146197</fpage><pub-id pub-id-type="pmid">26730961</pub-id></element-citation></ref><ref id="B71"><label>71</label><element-citation publication-type="journal"><name><surname>Yi</surname><given-names>L</given-names></name><name><surname>Li</surname><given-names>Z</given-names></name><name><surname>Yuan</surname><given-names>K</given-names></name><name><surname>Qu</surname><given-names>X</given-names></name><name><surname>Chen</surname><given-names>J</given-names></name><name><surname>Wang</surname><given-names>G</given-names></name><etal></etal><article-title>Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells</article-title><source>J Virol</source><year>2004</year><volume>78</volume><fpage>11334</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">15452254</pub-id></element-citation></ref><ref id="B72"><label>72</label><element-citation publication-type="journal"><name><surname>Schwarz</surname><given-names>S</given-names></name><name><surname>Wang</surname><given-names>K</given-names></name><name><surname>Yu</surname><given-names>WJ</given-names></name><name><surname>Sun</surname><given-names>B</given-names></name><name><surname>Schwarz</surname><given-names>W</given-names></name><article-title>Emodin inhibits current through SARS-associated coronavirus 3a protein</article-title><source>Antiviral res</source><year>2011</year><volume>90</volume><fpage>64</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">21356245</pub-id></element-citation></ref><ref id="B73"><label>73</label><element-citation publication-type="journal"><name><surname>Schwarz</surname><given-names>S</given-names></name><name><surname>Sauter</surname><given-names>D</given-names></name><name><surname>Wang</surname><given-names>K</given-names></name><name><surname>Zhang</surname><given-names>R</given-names></name><name><surname>Sun</surname><given-names>B</given-names></name><name><surname>Karioti</surname><given-names>A</given-names></name><etal></etal><article-title>Kaempferol Derivatives as Antiviral Drugs against the 3a Channel Protein of Coronavirus</article-title><source>Planta Medica</source><year>2014</year><volume>80</volume><fpage>177</fpage><lpage>82</lpage><pub-id pub-id-type="pmid">24458263</pub-id></element-citation></ref><ref id="B74"><label>74</label><element-citation publication-type="journal"><name><surname>Cheng</surname><given-names>PW</given-names></name><name><surname>Ng</surname><given-names>LT</given-names></name><name><surname>Chiang</surname><given-names>LC</given-names></name><name><surname>Lin</surname><given-names>CC</given-names></name><article-title>Antiviral effects of saikosaponins on human coronavirus 229E in vitro</article-title><source>Clin Exp Pharmacol Physiol</source><year>2006</year><volume>33</volume><fpage>612</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">16789928</pub-id></element-citation></ref><ref id="B75"><label>75</label><element-citation publication-type="other"><name><surname>Pilcher</surname><given-names>H</given-names></name><article-title>Liquorice may tackle SARS</article-title><source>Nature</source><year>2003</year></element-citation></ref><ref id="B76"><label>76</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>CJ</given-names></name><name><surname>Michaelis</surname><given-names>M</given-names></name><name><surname>Hsu</surname><given-names>HK</given-names></name><name><surname>Tsai</surname><given-names>CC</given-names></name><name><surname>Yang</surname><given-names>KD</given-names></name><name><surname>Wu</surname><given-names>YC</given-names></name><etal></etal><article-title>Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication</article-title><source>J Ethnopharmacol</source><year>2008</year><volume>120</volume><fpage>108</fpage><lpage>11</lpage><pub-id pub-id-type="pmid">18762235</pub-id></element-citation></ref><ref id="B77"><label>77</label><element-citation publication-type="other"><name><surname>Lu</surname><given-names>H</given-names></name><article-title>Drug treatment options for the 2019-new coronavirus (2019-nCoV)</article-title><source>Biosci Trends</source><year>2020</year></element-citation></ref><ref id="B78"><label>78</label><mixed-citation publication-type="other"><comment>Science CAo. Researchers in Shanghai Institute of Drugs and Wuhan Virus Institute discovered that the Chinese patent medicine Shuanghuanglian oral liquid can inhibit the 2019-new coronavirus.; 2020</comment></mixed-citation></ref><ref id="B79"><label>79</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Howard</surname><given-names>OM</given-names></name><name><surname>Yang</surname><given-names>X</given-names></name><name><surname>Wang</surname><given-names>L</given-names></name><name><surname>Oppenheim</surname><given-names>JJ</given-names></name><name><surname>Krakauer</surname><given-names>T</given-names></name><article-title>Effects of Shuanghuanglian and Qingkailing, two multi-components of traditional Chinese medicinal preparations, on human leukocyte function</article-title><source>Life Sci</source><year>2002</year><volume>70</volume><fpage>2897</fpage><lpage>913</lpage><pub-id pub-id-type="pmid">12269401</pub-id></element-citation></ref><ref id="B80"><label>80</label><element-citation publication-type="journal"><name><surname>Gao</surname><given-names>Y</given-names></name><name><surname>Fang</surname><given-names>L</given-names></name><name><surname>Cai</surname><given-names>R</given-names></name><name><surname>Zong</surname><given-names>C</given-names></name><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Lu</surname><given-names>J</given-names></name><etal></etal><article-title>Shuang-Huang-Lian exerts anti-inflammatory and anti-oxidative activities in lipopolysaccharide-stimulated murine alveolar macrophages</article-title><source>Phytomedicine</source><year>2014</year><volume>21</volume><fpage>461</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">24192210</pub-id></element-citation></ref><ref id="B81"><label>81</label><element-citation publication-type="journal"><name><surname>Chan</surname><given-names>MC</given-names></name><name><surname>Chan</surname><given-names>RW</given-names></name><name><surname>Mok</surname><given-names>CK</given-names></name><name><surname>Mak</surname><given-names>NK</given-names></name><name><surname>Wong</surname><given-names>RN</given-names></name><article-title>Indirubin-3'-oxime as an antiviral and immunomodulatory agent in treatment of severe human influenza virus infection</article-title><source>Hong Kong Med J</source><year>2018</year><volume>24</volume><issue>Suppl 6</issue><fpage>45</fpage><lpage>7</lpage></element-citation></ref><ref id="B82"><label>82</label><element-citation publication-type="journal"><name><surname>Ding</surname><given-names>Y</given-names></name><name><surname>Zeng</surname><given-names>L</given-names></name><name><surname>Li</surname><given-names>R</given-names></name><name><surname>Chen</surname><given-names>Q</given-names></name><name><surname>Zhou</surname><given-names>B</given-names></name><name><surname>Chen</surname><given-names>Q</given-names></name><etal></etal><article-title>The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function</article-title><source>BMC Complement Altern Med</source><year>2017</year><volume>17</volume><fpage>130</fpage><pub-id pub-id-type="pmid">28235408</pub-id></element-citation></ref><ref id="B83"><label>83</label><element-citation publication-type="journal"><name><surname>Dong</surname><given-names>L</given-names></name><name><surname>Xia</surname><given-names>JW</given-names></name><name><surname>Gong</surname><given-names>Y</given-names></name><name><surname>Chen</surname><given-names>Z</given-names></name><name><surname>Yang</surname><given-names>H-H</given-names></name><name><surname>Zhang</surname><given-names>J</given-names></name><etal></etal><article-title>Effect of Lianhuaqingwen Capsules on Airway Inflammation in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease</article-title><source>Evid Based Complement Alternat Med</source><year>2014</year><volume>2014</volume><fpage>1</fpage><lpage>11</lpage></element-citation></ref><ref id="B84"><label>84</label><element-citation publication-type="journal"><name><surname>Li</surname><given-names>S</given-names></name><name><surname>Chen</surname><given-names>C</given-names></name><name><surname>Zhang</surname><given-names>H</given-names></name><name><surname>Guo</surname><given-names>H</given-names></name><name><surname>Wang</surname><given-names>H</given-names></name><name><surname>Wang</surname><given-names>L</given-names></name><etal></etal><article-title>Identification of natural compounds with antiviral activities against SARS-associated coronavirus</article-title><source>Antiviral Res</source><year>2005</year><volume>67</volume><fpage>18</fpage><lpage>23</lpage><pub-id pub-id-type="pmid">15885816</pub-id></element-citation></ref><ref id="B85"><label>85</label><element-citation publication-type="journal"><name><surname>Chang</surname><given-names>FR</given-names></name><name><surname>Yen</surname><given-names>CT</given-names></name><name><surname>Ei-Shazly</surname><given-names>M</given-names></name><name><surname>Lin</surname><given-names>WH</given-names></name><name><surname>Yen</surname><given-names>MH</given-names></name><name><surname>Lin</surname><given-names>KH</given-names></name><etal></etal><article-title>Anti-Human Coronavirus (anti-HCoV) Triterpenoids from the Leaves of Euphorbia Neriifolia</article-title><source>Nat Prod Commun</source><year>2012</year><volume>7</volume><fpage>1934578X1200701103</fpage></element-citation></ref><ref id="B86"><label>86</label><element-citation publication-type="journal"><name><surname>Shen</surname><given-names>YC</given-names></name><name><surname>Wang</surname><given-names>LT</given-names></name><name><surname>Khalil</surname><given-names>AT</given-names></name><name><surname>Chiang</surname><given-names>LC</given-names></name><name><surname>Cheng</surname><given-names>PW</given-names></name><article-title>Bioactive Pyranoxanthones from the Roots of Calophyllum blancoi</article-title><source>Chem Pharm Bull</source><year>2005</year><volume>53</volume><fpage>244</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">15684529</pub-id></element-citation></ref><ref id="B87"><label>87</label><element-citation publication-type="other"><collab>National Health Commission of the People's Republic of China</collab><article-title>Transcript of press conference in 17, February, 2020</article-title><source>http://www.nhc.gov.cn/xcs/s3574/202002/f12a62d10c2a48c6895cedf2faea6e1f. shtml</source><year>2020</year></element-citation></ref><ref id="B88"><label>88</label><element-citation publication-type="other"><collab>National Health Commission of the People's Republic of China</collab><article-title>Notice on the issunance of guidelines of diagnosis and treatment for 2019-nCoV infected pneumonia (version 6)</article-title><source>6 ed; http://www.nhc.gov.cn/yzygj/s7653p/202002/8334a8326dd94d329df351d7da8aefc2.shtml?from=timeline</source><year>2020</year></element-citation></ref><ref id="B89"><label>89</label><element-citation publication-type="other"><name><surname>Han</surname><given-names>YY</given-names></name><name><surname>Zhao</surname><given-names>MR</given-names></name><name><surname>Shi</surname><given-names>B</given-names></name><name><surname>Song</surname><given-names>ZH</given-names></name><name><surname>Zhou</surname><given-names>SP</given-names></name><name><surname>He</surname><given-names>Y</given-names></name><article-title>Application of integrative medicine protocols on treatment of coronavirus disease 2019</article-title><source>Chi Tradit Herbal Drugs. 1-5</source></element-citation></ref><ref id="B90"><label>90</label><element-citation publication-type="other"><name><surname>Zhu</surname><given-names>YG</given-names></name><name><surname>Deng</surname><given-names>ZW</given-names></name><name><surname>Liu</surname><given-names>LH</given-names></name><name><surname>Liu</surname><given-names>XH</given-names></name><name><surname>Li</surname><given-names>XZ</given-names></name><name><surname>Chen</surname><given-names>WH</given-names></name><etal></etal><article-title>Compilation of drug information for the diagnosis and treatment of COVID-19 (version 1)</article-title><source>Central South Pharmacy. 1-14</source></element-citation></ref><ref id="B91"><label>91</label><element-citation publication-type="other"><name><surname>Xu</surname><given-names>X</given-names></name><name><surname>Zhang</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><name><surname>Li</surname><given-names>XX</given-names></name><article-title>Analysis on prevention plan of corona virus disease-19 (COVID-19) by traditional Chinese medicine in various regions</article-title><source>Chin Herb Med</source><year>2020</year><fpage>1</fpage><lpage>7</lpage></element-citation></ref><ref id="B92"><label>92</label><element-citation publication-type="other"><name><surname>Zhao</surname><given-names>J</given-names></name><name><surname>Tian</surname><given-names>SS</given-names></name><name><surname>Yang</surname><given-names>J</given-names></name><name><surname>Liu</surname><given-names>J</given-names></name><name><surname>Zhang</surname><given-names>WD</given-names></name><article-title>Investigating the mechanism of Qing-Fei-Pai-Du-Tang for the treatment of Novel Coronavirus Pneumonia by network pharmacology</article-title><source>Chin Herb Med</source><year>2020</year><fpage>1</fpage><lpage>7</lpage></element-citation></ref><ref id="B93"><label>93</label><element-citation publication-type="other"><name><surname>Yao</surname><given-names>KT</given-names></name><name><surname>Liu</surname><given-names>MY</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><name><surname>Huang</surname><given-names>JH</given-names></name><name><surname>Cai</surname><given-names>HB</given-names></name><article-title>Retrospective Clinical Analysis on Treatment of Novel Coronavirus-infected Pneumonia with Traditional Chinese Medicine Lianhua Qingwen</article-title><source>Chin J Exp Tradit Med Form</source><year>2020</year><fpage>1</fpage><lpage>7</lpage></element-citation></ref><ref id="B94"><label>94</label><element-citation publication-type="other"><name><surname>Lv</surname><given-names>RB</given-names></name><name><surname>Wang</surname><given-names>WJ</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><article-title>Treatment of suspected new coronavirus pneumonia with Chinese medicine Lianhua Qingwen Clinical observation of 63 suspected cases</article-title><source>J Tradit Chin Med</source><year>2020</year><fpage>1</fpage><lpage>5</lpage></element-citation></ref><ref id="B95"><label>95</label><element-citation publication-type="other"><name><surname>Zhang</surname><given-names>JW</given-names></name><name><surname>Hu</surname><given-names>X</given-names></name><name><surname>Jin</surname><given-names>PF</given-names></name><article-title>Cytokine storms caused by 2019-nCoV and drug therapy</article-title><source>Chinese Pharmaceutical Journal</source><year>2020</year><fpage>1</fpage><lpage>9</lpage><comment>96</comment></element-citation></ref><ref id="B96"><label>96</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Yang</surname><given-names>D</given-names></name><name><surname>Shen</surname><given-names>W</given-names></name><name><surname>Dong</surname><given-names>HF</given-names></name><name><surname>Wang</surname><given-names>JM</given-names></name><name><surname>Oppenheim</surname><given-names>JJ</given-names></name><etal></etal><article-title>Characterization of chenodeoxycholic acid as an endogenous antagonist of the G-coupled formyl peptide receptors</article-title><source>Inflamm Res</source><year>2000</year><volume>49</volume><fpage>744</fpage><lpage>55</lpage><pub-id pub-id-type="pmid">11211928</pub-id></element-citation></ref><ref id="B97"><label>97</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Mellon</surname><given-names>RD</given-names></name><name><surname>Yang</surname><given-names>L</given-names></name><name><surname>Dong</surname><given-names>H</given-names></name><name><surname>Oppenheim</surname><given-names>JJ</given-names></name><name><surname>Howard</surname><given-names>OM</given-names></name><article-title>Regulatory effects of deoxycholic acid, a component of the anti-inflammatory traditional Chinese medicine Niuhuang, on human leukocyte response to chemoattractants</article-title><source>Biochem Pharmacol</source><year>2002</year><volume>63</volume><fpage>533</fpage><lpage>41</lpage><pub-id pub-id-type="pmid">11853704</pub-id></element-citation></ref><ref id="B98"><label>98</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Beutler</surname><given-names>JA</given-names></name><name><surname>McCloud</surname><given-names>TG</given-names></name><name><surname>Loehfelm</surname><given-names>A</given-names></name><name><surname>Yang</surname><given-names>L</given-names></name><name><surname>Dong</surname><given-names>HF</given-names></name><etal></etal><article-title>Tannic acid is an inhibitor of CXCL12 (SDF-1alpha)/CXCR4 with antiangiogenic activity</article-title><source>Clin Cancer Res</source><year>2003</year><volume>9</volume><fpage>3115</fpage><lpage>23</lpage><pub-id pub-id-type="pmid">12912963</pub-id></element-citation></ref><ref id="B99"><label>99</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Yang</surname><given-names>L</given-names></name><name><surname>Zhang</surname><given-names>N</given-names></name><name><surname>Turpin</surname><given-names>JA</given-names></name><name><surname>Buckheit</surname><given-names>RW</given-names></name><name><surname>Osterling</surname><given-names>C</given-names></name><etal></etal><article-title>Shikonin, a component of chinese herbal medicine, inhibits chemokine receptor function and suppresses human immunodeficiency virus type 1</article-title><source>Antimicrob Agents Chemother</source><year>2003</year><volume>47</volume><fpage>2810</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">12936978</pub-id></element-citation></ref><ref id="B100"><label>100</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Oppenheim</surname><given-names>JJ</given-names></name><name><surname>Howard</surname><given-names>OM</given-names></name><article-title>Chemokines and chemokine receptors as novel therapeutic targets in rheumatoid arthritis (RA): inhibitory effects of traditional Chinese medicinal components</article-title><source>Cell Mol Immunol</source><year>2004</year><volume>1</volume><fpage>336</fpage><lpage>42</lpage><pub-id pub-id-type="pmid">16285892</pub-id></element-citation></ref><ref id="B101"><label>101</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Murakami</surname><given-names>T</given-names></name><name><surname>Oppenheim</surname><given-names>JJ</given-names></name><name><surname>Howard</surname><given-names>OM</given-names></name><article-title>Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking</article-title><source>Blood</source><year>2005</year><volume>106</volume><fpage>2409</fpage><lpage>16</lpage><pub-id pub-id-type="pmid">15956285</pub-id></element-citation></ref><ref id="B102"><label>102</label><element-citation publication-type="other"><name><surname>He</surname><given-names>J</given-names></name><name><surname>He</surname><given-names>ZD</given-names></name><name><surname>Chen</surname><given-names>X</given-names></name><article-title>Effects of Chinese medicinal components on chemokine receptors: theory, results and methodology</article-title><source>Evidence-based Research Methods for Chinese Medicine</source><year>2016</year><fpage>187</fpage><lpage>97</lpage></element-citation></ref><ref id="B103"><label>103</label><element-citation publication-type="journal"><name><surname>Chen</surname><given-names>YB</given-names></name><name><surname>Chen</surname><given-names>X</given-names></name><article-title>Ancient herbal component may be a novel therapeutic for gouty arthritis</article-title><source>J Leukoc Biol</source><year>2019</year><volume>105</volume><fpage>7</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">30517770</pub-id></element-citation></ref><ref id="B104"><label>104</label><element-citation publication-type="journal"><name><surname>Wang</surname><given-names>J</given-names></name><name><surname>Qiao</surname><given-names>LF</given-names></name><name><surname>Li</surname><given-names>YS</given-names></name><name><surname>Yang</surname><given-names>GT</given-names></name><article-title>Shen Fu injection activate the macrophage NF-kB of rats' alveolar induced by LPS</article-title><source>Acta Medicinae Universitatis Scientiae et Technologiae Huazhong</source><year>2009</year><volume>1</volume><fpage>15</fpage><lpage>8</lpage></element-citation></ref><ref id="B105"><label>105</label><element-citation publication-type="journal"><name><surname>Chang</surname><given-names>XJ</given-names></name><name><surname>Xiao</surname><given-names>W</given-names></name><name><surname>Zhang</surname><given-names>S</given-names></name><name><surname>Chang</surname><given-names>YP</given-names></name><name><surname>Chen</surname><given-names>CM</given-names></name><name><surname>Chen</surname><given-names>J</given-names></name><etal></etal><article-title>Mechanism of Re Du Ning injection on anti-acute lung injury in rats based on cytokines storm</article-title><source>Chin Herb Med</source><year>2014</year><volume>46</volume><fpage>236</fpage><lpage>9</lpage></element-citation></ref><ref id="B106"><label>106</label><element-citation publication-type="journal"><name><surname>Zou</surname><given-names>HM</given-names></name><name><surname>He</surname><given-names>TZ</given-names></name><name><surname>Chen</surname><given-names>X</given-names></name><article-title>Tetrandrine inhibits differentiation of proinflammatory subsets of T helper cells but spares de novo differentiation of iTreg cells</article-title><source>Int Immunopharmacol</source><year>2019</year><volume>69</volume><fpage>307</fpage><lpage>12</lpage><pub-id pub-id-type="pmid">30769211</pub-id></element-citation></ref><ref id="B107"><label>107</label><element-citation publication-type="other"><name><surname>Chen</surname><given-names>H</given-names></name><name><surname>Du</surname><given-names>Q</given-names></name><article-title>Potential Natural Compounds for Preventing 2019-nCoV Infection</article-title><source>Preprints</source><year>2020</year></element-citation></ref><ref id="B108"><label>108</label><element-citation publication-type="other"><name><surname>Ng</surname><given-names>AWT</given-names></name><name><surname>Poon</surname><given-names>SL</given-names></name><name><surname>Huang</surname><given-names>MN</given-names></name><name><surname>Lim</surname><given-names>JQ</given-names></name><name><surname>Boot</surname><given-names>A</given-names></name><name><surname>Yu</surname><given-names>W</given-names></name><etal></etal><article-title>Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia</article-title><source>Sci Trans Med</source><year>2017</year><comment>9</comment></element-citation></ref><ref id="B109"><label>109</label><element-citation publication-type="journal"><name><surname>Zeng</surname><given-names>ZP</given-names></name><name><surname>Jiang</surname><given-names>JG</given-names></name><article-title>Analysis of the adverse reactions induced by natural product-derived drugs</article-title><source>Br J Pharmacol</source><year>2010</year><volume>159</volume><fpage>1374</fpage><lpage>91</lpage><pub-id pub-id-type="pmid">20233209</pub-id></element-citation></ref><ref id="B110"><label>110</label><element-citation publication-type="journal"><name><surname>Fugh-Berman</surname><given-names>A</given-names></name><article-title>Herb-drug interactions</article-title><source>Lancet</source><year>2000</year><volume>355</volume><fpage>134</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">10675182</pub-id></element-citation></ref><ref id="B111"><label>111</label><element-citation publication-type="journal"><name><surname>Liu</surname><given-names>LS</given-names></name><name><surname>Lei</surname><given-names>N</given-names></name><name><surname>Lin</surname><given-names>Q</given-names></name><name><surname>Wang</surname><given-names>WL</given-names></name><name><surname>Yan</surname><given-names>HW</given-names></name><name><surname>Duan</surname><given-names>XH</given-names></name><article-title>The Effects and Mechanism of Yinqiao Powder on Upper Respiratory Tract Infection</article-title><source>Int J Biotechnol Wellness Ind</source><year>2015</year><volume>4</volume><fpage>57</fpage><lpage>60</lpage></element-citation></ref><ref id="B112"><label>112</label><element-citation publication-type="journal"><name><surname>Fu</surname><given-names>YJ</given-names></name><name><surname>Yan</surname><given-names>YQ</given-names></name><name><surname>Qin</surname><given-names>HQ</given-names></name><name><surname>Wu</surname><given-names>S</given-names></name><name><surname>Shi</surname><given-names>SS</given-names></name><name><surname>Zheng</surname><given-names>X</given-names></name><etal></etal><article-title>Effects of different principles of Traditional Chinese Medicine treatment on TLR7/NF-κB signaling pathway in influenza virus infected mice</article-title><source>Chin Med</source><year>2018</year><volume>13</volume><fpage>42</fpage><pub-id pub-id-type="pmid">30151032</pub-id></element-citation></ref><ref id="B113"><label>113</label><element-citation publication-type="journal"><name><surname>Lau</surname><given-names>JT</given-names></name><name><surname>Leung</surname><given-names>PC</given-names></name><name><surname>Wong</surname><given-names>EL</given-names></name><name><surname>Fong</surname><given-names>C</given-names></name><name><surname>Cheng</surname><given-names>KF</given-names></name><name><surname>Zhang</surname><given-names>SC</given-names></name><etal></etal><article-title>The use of an herbal formula by hospital care workers during the severe acute respiratory syndrome epidemic in Hong Kong to prevent severe acute respiratory syndrome transmission, relieve influenza-related symptoms, and improve quality of life: a prospective cohort study</article-title><source>J Altern Complement Med</source><year>2005</year><volume>11</volume><fpage>49</fpage><lpage>55</lpage><pub-id pub-id-type="pmid">15750363</pub-id></element-citation></ref><ref id="B114"><label>114</label><element-citation publication-type="journal"><name><surname>Du</surname><given-names>CY</given-names></name><name><surname>Zheng</surname><given-names>KY</given-names></name><name><surname>Bi</surname><given-names>CW</given-names></name><name><surname>Dong</surname><given-names>TT</given-names></name><name><surname>Lin</surname><given-names>H</given-names></name><name><surname>Tsim</surname><given-names>KW</given-names></name><article-title>Yu Ping Feng San, an Ancient Chinese Herbal Decoction, Induces Gene Expression of Anti-viral Proteins and Inhibits Neuraminidase Activity</article-title><source>Phytother Res</source><year>2015</year><volume>29</volume><fpage>656</fpage><lpage>61</lpage><pub-id pub-id-type="pmid">25586308</pub-id></element-citation></ref><ref id="B115"><label>115</label><element-citation publication-type="journal"><name><surname>Gao</surname><given-names>J</given-names></name><name><surname>Li</surname><given-names>J</given-names></name><name><surname>Shao</surname><given-names>X</given-names></name><name><surname>Jin</surname><given-names>Y</given-names></name><name><surname>Lu</surname><given-names>XW</given-names></name><name><surname>Ge</surname><given-names>JF</given-names></name><etal></etal><article-title>Antiinflammatory and immunoregulatory effects of total glucosides of Yupingfeng powder</article-title><source>Chin Med J (Engl)</source><year>2009</year><volume>122</volume><fpage>1636</fpage><lpage>41</lpage><pub-id pub-id-type="pmid">19719964</pub-id></element-citation></ref><ref id="B116"><label>116</label><element-citation publication-type="journal"><name><surname>Zhang</surname><given-names>H</given-names></name><name><surname>Chen</surname><given-names>Q</given-names></name><name><surname>Zhou</surname><given-names>W</given-names></name><name><surname>Gao</surname><given-names>S</given-names></name><name><surname>Lin</surname><given-names>H</given-names></name><name><surname>Ye</surname><given-names>S</given-names></name><etal></etal><article-title>Chinese medicine injection shuanghuanglian for treatment of acute upper respiratory tract infection: a systematic review of randomized controlled trials</article-title><source>Evid Based Complement Alternat Med</source><year>2013</year><volume>2013</volume><fpage>987326</fpage><pub-id pub-id-type="pmid">23606893</pub-id></element-citation></ref><ref id="B117"><label>117</label><element-citation publication-type="other"><name><surname>Xiao</surname><given-names>GL</given-names></name><name><surname>Song</surname><given-names>K</given-names></name><name><surname>Yuan CJ</surname><given-names>ea</given-names></name><article-title>A literature report on the treatment of SARS by stages with traditional Chinese medicine</article-title><source>J Emerg Chin Med Hunan</source><year>2005</year><fpage>53</fpage><lpage>5</lpage></element-citation></ref><ref id="B118"><label>118</label><element-citation publication-type="journal"><name><surname>Bao</surname><given-names>L</given-names></name><name><surname>J</surname><given-names>M</given-names></name><article-title>Research progress of Da Yuan Yin on the treatment of infectious diseases</article-title><source>Emerg Tradit Chin Med</source><year>2010</year><volume>2</volume><fpage>263</fpage><lpage>87</lpage></element-citation></ref><ref id="B119"><label>119</label><element-citation publication-type="journal"><name><surname>Kim</surname><given-names>DE</given-names></name><name><surname>Min</surname><given-names>JS</given-names></name><name><surname>Jang</surname><given-names>MS</given-names></name><name><surname>Lee</surname><given-names>JY</given-names></name><name><surname>Shin</surname><given-names>YS</given-names></name><name><surname>Song</surname><given-names>JH</given-names></name><etal></etal><article-title>Natural Bis-Benzylisoquinoline Alkaloids-Tetrandrine, Fangchinoline, and Cepharanthine, Inhibit Human Coronavirus OC43 Infection of MRC-5 Human Lung Cells</article-title><source>Biomolecules</source><year>2019</year><volume>9</volume><fpage>696</fpage></element-citation></ref></ref-list></back><floats-group><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Conventional treatment of patients with SARS-CoV-2 infection</p></caption><table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">Type of treatment</th><th rowspan="1" colspan="1">Therapeutic agent or device</th><th rowspan="1" colspan="1">Reference</th></tr></thead><tbody valign="top"><tr><td rowspan="1" colspan="1"><bold>Oxygen therapy</bold><break></break><break></break></td><td rowspan="1" colspan="1">Nasal cannula<break></break>Non-invasive mechanical ventilation<break></break>Invasive mechanical ventilation<break></break>ECMO*</td><td rowspan="1" colspan="1"><xref rid="B16" ref-type="bibr">16</xref></td></tr><tr><td rowspan="1" colspan="1"><bold>Antibiotics combination</bold></td><td rowspan="1" colspan="1">Amoxicillin<break></break>Azithromycin<break></break>Fluoroquinolones</td><td rowspan="1" colspan="1"><xref rid="B16" ref-type="bibr">16</xref></td></tr><tr><td rowspan="7" colspan="1"><bold>Antivirals</bold><break></break><break></break><break></break></td><td rowspan="1" colspan="1">Lopinavir/ ritonavir</td><td rowspan="1" colspan="1"><xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B17" ref-type="bibr">17</xref></td></tr><tr><td rowspan="1" colspan="1">Ribavirin</td><td rowspan="1" colspan="1"><xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B18" ref-type="bibr">18</xref></td></tr><tr><td rowspan="1" colspan="1">Favipiravir (T-705)</td><td rowspan="1" colspan="1"><xref rid="B19" ref-type="bibr">19</xref>, <xref rid="B20" ref-type="bibr">20</xref></td></tr><tr><td rowspan="1" colspan="1">Remdesivir</td><td rowspan="1" colspan="1"><xref rid="B20" ref-type="bibr">20</xref>-<xref rid="B23" ref-type="bibr">23</xref></td></tr><tr><td rowspan="1" colspan="1">Oseltamivir</td><td rowspan="1" colspan="1"><xref rid="B7" ref-type="bibr">7</xref></td></tr><tr><td rowspan="1" colspan="1">Chloroquine</td><td rowspan="1" colspan="1"><xref rid="B20" ref-type="bibr">20</xref>, <xref rid="B36" ref-type="bibr">36</xref></td></tr><tr><td rowspan="1" colspan="1">Interferon</td><td rowspan="1" colspan="1"><xref rid="B7" ref-type="bibr">7</xref>, <xref rid="B17" ref-type="bibr">17</xref></td></tr><tr><td rowspan="1" colspan="1"><bold>Corticosteroids</bold></td><td rowspan="1" colspan="1">Methylprednisolone</td><td rowspan="1" colspan="1"><xref rid="B7" ref-type="bibr">7</xref></td></tr><tr><td rowspan="1" colspan="1"><bold>Convalescent plasma</bold></td><td rowspan="1" colspan="1">Convalescent plasma</td><td rowspan="1" colspan="1"><xref rid="B22" ref-type="bibr">22</xref></td></tr></tbody></table><table-wrap-foot><fn><p>*ECMO, extracorporeal membrane oxygenation.</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float"><label>Table 2</label><caption><p>TCM herb formulae used for the Treatment of SARS-CoV infection</p></caption><table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">TCM Formula</th><th rowspan="1" colspan="1">Composition</th><th rowspan="1" colspan="1">Therapeutics effect</th><th rowspan="1" colspan="1">Reference</th></tr></thead><tbody valign="top"><tr><td rowspan="1" colspan="1"><italic>Yin Qiao San</italic></td><td rowspan="1" colspan="1"><italic>Fructus Forsythiae, Flos Lonicerae, Radix Platycodonis, Herba Menthae, Herba Lophatheri, Radix Glycyrrhizae, Herba Schizonepetae,</italic> Fermented soybean<italic>, Fructus arctii,</italic> and<italic> Rhizoma Phragmitis</italic></td><td rowspan="1" colspan="1">“Disperses wind-heat, clears heat, and relieves toxicity”, according to TCM theory<break></break>Treatment of upper respiratory tract infection.<break></break>Improvement of the function of upper respiratory mucosal immune system</td><td rowspan="1" colspan="1"><xref rid="B111" ref-type="bibr">111</xref>, <xref rid="B112" ref-type="bibr">112</xref></td></tr><tr><td rowspan="1" colspan="1"><italic>Yu Ping Feng San</italic></td><td rowspan="1" colspan="1"><italic>Astragali radix, Astragalus membranaceus, Atractylodes macrocephala, and Saposhnikoviae Radix</italic></td><td rowspan="1" colspan="1">“Tonifying <italic>qi</italic>” to protect from external pathogens”, according to TCM theory<break></break>Reportedly have antiviral, anti-inflammatory and immunoregulatory effects</td><td rowspan="1" colspan="1"><xref rid="B113" ref-type="bibr">113</xref>-<xref rid="B115" ref-type="bibr">115</xref></td></tr><tr><td rowspan="1" colspan="1"><italic>Sang Ju Yin</italic> and <italic>Yu Ping Feng San</italic></td><td rowspan="1" colspan="1"><italic>Sang Ju Yin</italic> [made with <italic>chrysanthemum, mulberry leaf</italic>, and 6 other herbs] and <italic>Yu Ping Feng San</italic></td><td rowspan="1" colspan="1">Reportedly have anti-viral and immunoregulatory effects</td><td rowspan="1" colspan="1"><xref rid="B46" ref-type="bibr">46</xref></td></tr><tr><td rowspan="1" colspan="1"><italic>Lian Hua Qing Wen Capsule</italic><break></break></td><td rowspan="1" colspan="1"><italic>Forsythia suspensa</italic>, <italic>Ephedra sinica, Lonicera japonica, Isatis indigotica, Mentha haplocalyx, Dryopteris crassirhizoma, Rhodiola rosea, Gypsum Fibrosum</italic>, <italic>Pogostemon cablin, Rheum palmatum</italic> , <italic>Houttuynia cordata, Glycyrrhizae, uralensis,</italic> and<italic> Armeniaca sibirica</italic></td><td rowspan="1" colspan="1">“Clear heat and detoxify, removes lung hotness”, according to TCM theory<break></break>Reportedly have antiviral, anti-inflammatory and immunoregulatory effects.</td><td rowspan="1" colspan="1"><xref rid="B82" ref-type="bibr">82</xref>, <xref rid="B83" ref-type="bibr">83</xref></td></tr><tr><td rowspan="1" colspan="1">S<italic>huang Huang Lian</italic></td><td rowspan="1" colspan="1"><italic>Lonicera japonica, Scutellaria baicalensis,</italic> and <italic>Forsythia suspensa</italic></td><td rowspan="1" colspan="1">“Clear heat and detoxify, remove lung hotness”, according to TCM theory<break></break>Reportedly has anti-SARS-CoV-2 activity<break></break>Reportedly has immunosuppressive effects</td><td rowspan="1" colspan="1"><xref rid="B78" ref-type="bibr">78</xref>, <xref rid="B80" ref-type="bibr">80</xref>, <xref rid="B116" ref-type="bibr">116</xref></td></tr><tr><td rowspan="1" colspan="1"><italic>Ma Xin Gan Shi Tang</italic><break></break></td><td rowspan="1" colspan="1"><italic>Ephedrae herba, Armeniacae semenamarum</italic>), <italic>Glycyrrhizae radix et rhizome, Gypsum fibrosum,</italic> and <italic>Da Yuan Yin [Arecae semen, Magnoliae officinalis cortex, Tsaoko fructus,Anemarrhenae rhizoma, Dioscoreae rhizoma, Scutellariae radix,</italic> and<italic> Glycyrrhizae raadix et rhizome]</italic></td><td rowspan="1" colspan="1">“Facilitate the flow of the lung “<italic>qi”</italic> and clear away heat”, according to TCM theory<break></break>Reportedly have anti-SARS-CoV activity</td><td rowspan="1" colspan="1"><xref rid="B117" ref-type="bibr">117</xref>, <xref rid="B118" ref-type="bibr">118</xref></td></tr></tbody></table></table-wrap><table-wrap id="T3" position="float"><label>Table 3</label><caption><p>TCM herbal extracts or TCM-derived Compounds with anti-HCoV Activity</p></caption><table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">TCM Compound (s)</th><th rowspan="1" colspan="1">Mode of action</th><th rowspan="1" colspan="1">Reference</th></tr></thead><tbody valign="top"><tr><td rowspan="1" colspan="1">Plant-derived phenolic compounds and Root extract of <italic>Isatis indigotica</italic></td><td rowspan="1" colspan="1">Inhibit the cleavage activity of SARS-3CLpro enzyme</td><td rowspan="1" colspan="1"><xref rid="B57" ref-type="bibr">57</xref></td></tr><tr><td rowspan="1" colspan="1">Water extract of <italic>Houttuynia cordata</italic></td><td rowspan="1" colspan="1">Inhibit the viral SARS-3CLpro activity<break></break>Block viral RNA‑dependent RNA polymerase activity (RdRp)<break></break>Immunomodulation</td><td rowspan="1" colspan="1"><xref rid="B54" ref-type="bibr">54</xref>, <xref rid="B55" ref-type="bibr">55</xref></td></tr><tr><td rowspan="1" colspan="1">Scutellarein and myricetin</td><td rowspan="1" colspan="1">Inhibit nsP13 by affecting the ATPase activity</td><td rowspan="1" colspan="1"><xref rid="B61" ref-type="bibr">61</xref></td></tr><tr><td rowspan="1" colspan="1">Glycyrrhizin from <italic>Glycyrrhizae radix</italic></td><td rowspan="1" colspan="1">Inhibit viral adsorption and penetration</td><td rowspan="1" colspan="1"><xref rid="B48" ref-type="bibr">48</xref>, <xref rid="B75" ref-type="bibr">75</xref></td></tr><tr><td rowspan="1" colspan="1">Herbacetin, quercetin, isobavaschalcone, 3‐β‐D‐glucoside and helichrysetin</td><td rowspan="1" colspan="1">Inhibit cleavage activity of MERS-3CLpro enzyme</td><td rowspan="1" colspan="1"><xref rid="B60" ref-type="bibr">60</xref></td></tr><tr><td rowspan="1" colspan="1">Tetrandrine, fangchinoline, and cepharanthine</td><td rowspan="1" colspan="1">Inhibit the expression of HCoV- OC43 spike and nucleocapsid protein.<break></break>Immunomodulation</td><td rowspan="1" colspan="1"><xref rid="B106" ref-type="bibr">106</xref>, <xref rid="B119" ref-type="bibr">119</xref></td></tr><tr><td rowspan="1" colspan="1">Chinese Rhubarb extracts</td><td rowspan="1" colspan="1">Inhibit SARS-3CLpro activity</td><td rowspan="1" colspan="1"><xref rid="B53" ref-type="bibr">53</xref></td></tr><tr><td rowspan="1" colspan="1">Flavonoids (For example: extracted from litchi seeds, herbacetin, rhoifolin, pectolinarin, quercetin, epigallocatechin gallate, and gallocatechin gallate)</td><td rowspan="1" colspan="1">Inhibit SARS-3CLpro activity</td><td rowspan="1" colspan="1"><xref rid="B56" ref-type="bibr">56</xref>, <xref rid="B58" ref-type="bibr">58</xref>, <xref rid="B59" ref-type="bibr">59</xref></td></tr><tr><td rowspan="1" colspan="1">Quercetin and TSL-1 from <italic>Toona sinensis</italic> Roem</td><td rowspan="1" colspan="1">Inhibit the cellular entry of SARS-CoV</td><td rowspan="1" colspan="1"><xref rid="B76" ref-type="bibr">76</xref></td></tr><tr><td rowspan="1" colspan="1">Emodin derived from genus <italic>Rheum</italic> and <italic>Polygonum</italic></td><td rowspan="1" colspan="1">Inhibit interaction of SARS-CoV Spike protein and ACE2<break></break>Inhibit the 3a ion channel of coronavirus SARS‐CoV and HCoV‐OC43</td><td rowspan="1" colspan="1"><xref rid="B67" ref-type="bibr">67</xref>, <xref rid="B72" ref-type="bibr">72</xref></td></tr><tr><td rowspan="1" colspan="1">Kaempferol derivatives</td><td rowspan="1" colspan="1">Inhibit 3a ion channel of coronavirus</td><td rowspan="1" colspan="1"><xref rid="B73" ref-type="bibr">73</xref></td></tr><tr><td rowspan="1" colspan="1">Baicalin from <italic>Scutellaria baicalensis</italic></td><td rowspan="1" colspan="1">Inhibit Angiotensin-converting enzyme (ACE)</td><td rowspan="1" colspan="1"><xref rid="B44" ref-type="bibr">44</xref>, <xref rid="B68" ref-type="bibr">68</xref></td></tr><tr><td rowspan="1" colspan="1">Saikosaponins</td><td rowspan="1" colspan="1">Prevent the early stage of HCoV‑22E9 infection, including viral attachment and penetration</td><td rowspan="1" colspan="1"><xref rid="B74" ref-type="bibr">74</xref></td></tr><tr><td rowspan="1" colspan="1">Tetra-<italic>O</italic>-galloyl-β-D-glucose and luteolin, from <italic>Galla chinensis</italic> and<italic> Veronicalina riifolia</italic> respectively</td><td rowspan="1" colspan="1">Avidly binds with surface spike protein of SARS-CoV</td><td rowspan="1" colspan="1"><xref rid="B71" ref-type="bibr">71</xref></td></tr></tbody></table></table-wrap><table-wrap id="T4" position="float"><label>Table 4</label><caption><p>Ongoing TCM Clinical Trials for the treatment of SARS-CoV-2 infection</p></caption><table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">Registration<break></break>number</th><th rowspan="1" colspan="1">Design type</th><th rowspan="1" colspan="1">Title</th><th rowspan="1" colspan="1">TCM herbal medicine</th><th rowspan="1" colspan="1">Sample size</th><th rowspan="1" colspan="1">Phase</th></tr></thead><tbody valign="top"><tr><td rowspan="1" colspan="1">ChiCTR2000029432</td><td rowspan="1" colspan="1">CCT</td><td rowspan="1" colspan="1">A real world study for the efficacy and safety of large dose Tanreqing Injection in the treatment of patients with novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Tan Re Qing Injection</italic></td><td rowspan="1" colspan="1">72</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029434</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">A randomized, open-label, blank-controlled trial for Lian-Hua Qing-Wen Capsule/Granule in the treatment of novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Lian Hua Qing Wen Capsule/Granule</italic></td><td rowspan="1" colspan="1">400</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029487</td><td rowspan="1" colspan="1">CCT</td><td rowspan="1" colspan="1">Clinical study for Gu-Biao Jie-Du-Ling in preventing of novel coronavirus pneumonia (COVID-19) in children</td><td rowspan="1" colspan="1"><italic>Gu Biao Jie Du Ling</italic></td><td rowspan="1" colspan="1">200</td><td rowspan="1" colspan="1">0</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029589</td><td rowspan="1" colspan="1">CCT</td><td rowspan="1" colspan="1">An open, prospective, multicenter clinical study for the efficacy and safety of Reduning injection in the treatment of ovel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Re Du Ning</italic><break></break><italic>Injection</italic></td><td rowspan="1" colspan="1">60</td><td rowspan="1" colspan="1">0</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029605</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">A randomized, open-label, blank-controlled, multicenter trial for Shuang-Huang-Lian oral solution in the treatment of novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Shuang Huang Lian Oral Liquid</italic></td><td rowspan="1" colspan="1">400</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029780</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">A multicenter, randomized, open, controlled trial for the efficacy and safety of Shen-Qi Fu-Zheng injection in the treatment of novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Shen Qi Fu Zheng Injection</italic></td><td rowspan="1" colspan="1">160</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029781</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">A multicenter, randomized, open and controlled trial for the efficacy and safety of Kang-Bing-Du granules in the treatment of novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Kang Bing Du Granules</italic></td><td rowspan="1" colspan="1">160</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029822</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">A randomized controlled trial for honeysuckle decoction in the treatment of patients with novel coronavirus (COVID-19) infection</td><td rowspan="1" colspan="1"><italic>Jin Yin Hua Tang</italic></td><td rowspan="1" colspan="1">110</td><td rowspan="1" colspan="1">0</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029991</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">A randomized, open-label, controlled trial for the safety and efficiency of Kesuting syrup and Keqing capsule in the treatment of mild and moderate novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Ke Su Ting Syrup</italic><break></break><italic>/Ke Qing Capsule</italic></td><td rowspan="1" colspan="1">72</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000030043</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">Shen-Fu injection in the treatment of severe novel coronavirus pneumonia (COVID-19): a multicenter, randomized, open-label, controlled trial</td><td rowspan="1" colspan="1"><italic>Shen Fu Injection</italic></td><td rowspan="1" colspan="1">300</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000030117</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">A multicenter, randomized, open, parallel controlled trial for the evaluation of the effectiveness and safety of Xiyanping injection in the treatment of common type novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Xi Yan Ping Injection</italic></td><td rowspan="1" colspan="1">348</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000030255</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">Efficacy and safety of Jing-Yin Granule in the treatment of novel coronavirus pneumonia (COVID-19) wind-heat syndrome</td><td rowspan="1" colspan="1"><italic>Jing Yin Granule</italic></td><td rowspan="1" colspan="1">300</td><td rowspan="1" colspan="1">4</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000030388</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">Efficacy and safety of Xue-Bi-Jing injection in the treatment of severe cases of novel coronavirus pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Xue Bi Jing Injection</italic></td><td rowspan="1" colspan="1">60</td><td rowspan="1" colspan="1">0</td></tr><tr><td rowspan="1" colspan="1">ChiCTR2000029813</td><td rowspan="1" colspan="1">RCT</td><td rowspan="1" colspan="1">Clinical Trial for Tanreqing Capsules in the Treatment of Novel Coronavirus Pneumonia (COVID-19)</td><td rowspan="1" colspan="1"><italic>Tan Re Qing Capsules</italic></td><td rowspan="1" colspan="1">72</td><td rowspan="1" colspan="1">0</td></tr></tbody></table><table-wrap-foot><fn><p>Notes: RCT: randomized controlled trial; CCT: controlled clinical trial.</p></fn></table-wrap-foot></table-wrap><table-wrap id="T5" position="float"><label>Table 5</label><caption><p>TCM recommended by 6th editions Guidelines of Diagnosis and Treatment for COVID-19 <xref rid="B88" ref-type="bibr">88</xref>.</p></caption><table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">Stage of disease</th><th rowspan="1" colspan="1">Symptom</th><th rowspan="1" colspan="1">Recommended Chinese patent medicine</th></tr></thead><tbody valign="top"><tr><td rowspan="2" colspan="1"><bold>Medical observation period</bold></td><td rowspan="1" colspan="1">Fatigue with gastrointestinal discomfort</td><td rowspan="1" colspan="1"><italic>Huo Xiang Zheng Qi Shui</italic></td></tr><tr><td rowspan="1" colspan="1">Fatigue with fever</td><td rowspan="1" colspan="1"><italic>Lian Hua Qing Wen Capsule, Shu Feng Jie Du Capsule, Jin Hua Qing Gan Capsule</italic></td></tr><tr><td rowspan="4" colspan="1"><bold>Clinical treatment period</bold><break></break><bold>(Confirmed patients)</bold></td><td rowspan="1" colspan="1">Mild cases</td><td rowspan="1" colspan="1"><italic>Qing Fei Pai Du Tang</italic></td></tr><tr><td rowspan="1" colspan="1">General cases</td><td rowspan="1" colspan="1"><italic>Qing Fei Pai Du Tang</italic></td></tr><tr><td rowspan="1" colspan="1">Several cases</td><td rowspan="1" colspan="1"><italic>Xi Yan Ping Injection, Xue Bi Jing Injection, Re Du Ning Injection, Tan Re Qing Injection, Xing Nao Jing Injection, Qing Fei Pai Du Tang</italic></td></tr><tr><td rowspan="1" colspan="1">Critical cases</td><td rowspan="1" colspan="1"><italic>Xue Bi Jing Injection, Re Du Ning Injection, Tan Re Qing Injection, Shen Fu Injection, Sheng Mai Injection, Shen Mai Injection, Su He Xiang Pill, An Gong Niu Huang Pill</italic></td></tr></tbody></table></table-wrap><table-wrap id="T6" position="float"><label>Table 6</label><caption><p>Frequently used TCM herbs for the Prevention of COVID-19 infection</p></caption><table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1">Reported by</th><th rowspan="1" colspan="1">Herbs (Latin name)</th><th rowspan="1" colspan="1">Herbs (Chinese Pin Yin)</th><th rowspan="1" colspan="1">Applicable regions</th></tr></thead><tbody valign="top"><tr><td rowspan="10" colspan="1"><bold>Luo, <italic>et al</italic>. <xref rid="B37" ref-type="bibr">37</xref></bold></td><td rowspan="1" colspan="1"><italic>Astragalus membranaceus</italic></td><td rowspan="1" colspan="1">Huangqi</td><td rowspan="10" colspan="1">23 provinces covered Northeast, North, Central (including Wuhan), South, East, Northwest, and Southwest China.</td></tr><tr><td rowspan="1" colspan="1"><italic>Glycyrrhizae uralensis</italic></td><td rowspan="1" colspan="1">Gancao</td></tr><tr><td rowspan="1" colspan="1"><italic>Saposhnikoviae divaricata</italic></td><td rowspan="1" colspan="1">Fangfeng</td></tr><tr><td rowspan="1" colspan="1"><italic>Rhizoma Atractylodis Macrocephalae</italic></td><td rowspan="1" colspan="1">Baizhu</td></tr><tr><td rowspan="1" colspan="1"><italic>Lonicerae Japonicae Flos</italic></td><td rowspan="1" colspan="1">Jinyinhua</td></tr><tr><td rowspan="1" colspan="1"><italic>Fructus Forsythiae</italic></td><td rowspan="1" colspan="1">Lianqiao</td></tr><tr><td rowspan="1" colspan="1"><italic>Atractylodis Rhizoma</italic></td><td rowspan="1" colspan="1">Cangzhu</td></tr><tr><td rowspan="1" colspan="1"><italic>Radix platycodonis</italic></td><td rowspan="1" colspan="1">Jiegeng</td></tr><tr><td rowspan="1" colspan="1"><italic>Agastache rugosa</italic></td><td rowspan="1" colspan="1">Huoxiang</td></tr><tr><td rowspan="1" colspan="1"><italic>Cyrtomium fortune J. Sm</italic></td><td rowspan="1" colspan="1">Guanzhong</td></tr><tr><td rowspan="9" colspan="1"><bold>Xu, <italic>et al.</italic><xref rid="B91" ref-type="bibr">91</xref></bold></td><td rowspan="1" colspan="1"><italic>Astragalus membranaceus</italic></td><td rowspan="1" colspan="1">Huangqi</td><td rowspan="1" colspan="1">Beijing, Tianjin, Shandong, Shaanxi, Gansu, Hebei, Shanxi, Henan, Hubei, Jiangxi, Hunan, and Yunnan</td></tr><tr><td rowspan="1" colspan="1"><italic>Atractylodis Rhizoma</italic></td><td rowspan="1" colspan="1">Cangzhu</td><td rowspan="3" colspan="1">Five regions in southern China (Hubei, Jiangxi, Hunan, Yunnan, and Wuhan)</td></tr><tr><td rowspan="1" colspan="1"><italic>Eupatorii Herba</italic></td><td rowspan="1" colspan="1">Peilan</td></tr><tr><td rowspan="1" colspan="1"><italic>Agastache rugosa</italic></td><td rowspan="1" colspan="1">Huoxiang</td></tr><tr><td rowspan="1" colspan="1"><italic>Ophiopogon japonicas</italic></td><td rowspan="1" colspan="1">Maidong</td><td rowspan="5" colspan="1">Eight regions in northern China (Beijing, Tianjin, Hebei, Henan, Shaanxi, Shanxi, Gansu, and Shandong)</td></tr><tr><td rowspan="1" colspan="1"><italic>Scrophularia ningpoensis</italic></td><td rowspan="1" colspan="1">Xuanshen</td></tr><tr><td rowspan="1" colspan="1"><italic>Rhizoma phragmitis</italic></td><td rowspan="1" colspan="1">Lugen</td></tr><tr><td rowspan="1" colspan="1"><italic>Adeinophora stricta Miq</italic></td><td rowspan="1" colspan="1">Shashen</td></tr><tr><td rowspan="1" colspan="1"><italic>Dendrobium nobile Lindl.</italic></td><td rowspan="1" colspan="1">Shihu</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001795 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001795 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |