Discovery of Hydrocarbon-Stapled Short α-Helical Peptides as Promising Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Fusion Inhibitors
Identifieur interne : 000599 ( Pmc/Checkpoint ); précédent : 000598; suivant : 000600Discovery of Hydrocarbon-Stapled Short α-Helical Peptides as Promising Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Fusion Inhibitors
Auteurs : Chao Wang [République populaire de Chine] ; Shuai Xia [République populaire de Chine] ; Peiyu Zhang [République populaire de Chine] ; Tianhong Zhang [République populaire de Chine] ; Weicong Wang [République populaire de Chine] ; Yangli Tian [République populaire de Chine] ; Guangpeng Meng [République populaire de Chine] ; Shibo Jiang [République populaire de Chine, États-Unis] ; Keliang Liu [République populaire de Chine]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2018.
Abstract
The hexameric α-helical coiled-coil formed between the C-terminal and N-terminal heptad repeat (CHR and NHR) regions of class I viral fusion proteins plays an important role in mediating the fusion of the viral and cellular membranes and provides a clear starting point for molecular mimicry that drives viral fusion inhibitor design. Unfortunately, such peptide mimicry of the short α-helical region in the CHR of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein has been thwarted by the loss of the peptide’s native α-helical conformation when taken out of the parent protein structure. Here, we describe that appropriate all-hydrocarbon stapling of the short helical portion-based peptide to reinforce its bioactive secondary structure remarkably improves antiviral potency. The resultant stapled peptide P21S10 could effectively inhibit infection by MERS-CoV pseudovirus and its spike protein-mediated cell–cell fusion; additionally, P21S10 exhibits improved pharmacokinetic properties than HR2P-M2, suggesting strong potential for development as an anti-MERS-CoV therapeutic.
Url:
DOI: 10.1021/acs.jmedchem.7b01732
PubMed: 29442512
PubMed Central: 7075646
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:7075646Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Discovery of Hydrocarbon-Stapled
Short α-Helical
Peptides as Promising Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) Fusion Inhibitors</title><author><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Peiyu" sort="Zhang, Peiyu" uniqKey="Zhang P" first="Peiyu" last="Zhang">Peiyu Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Tianhong" sort="Zhang, Tianhong" uniqKey="Zhang T" first="Tianhong" last="Zhang">Tianhong Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weicong" sort="Wang, Weicong" uniqKey="Wang W" first="Weicong" last="Wang">Weicong Wang</name><affiliation wicri:level="1"><nlm:aff id="aff5">Pharmaceutical Preparation Section, Plastic Surgery Hospital,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100144,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tian, Yangli" sort="Tian, Yangli" uniqKey="Tian Y" first="Yangli" last="Tian">Yangli Tian</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meng, Guangpeng" sort="Meng, Guangpeng" uniqKey="Meng G" first="Guangpeng" last="Meng">Guangpeng Meng</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Lindsley F. Kimball Research Institute,<institution>New York Blood Center</institution>, New York, New York 10065,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Keliang" sort="Liu, Keliang" uniqKey="Liu K" first="Keliang" last="Liu">Keliang Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29442512</idno><idno type="pmc">7075646</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075646</idno><idno type="RBID">PMC:7075646</idno><idno type="doi">10.1021/acs.jmedchem.7b01732</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000130</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000130</idno><idno type="wicri:Area/Pmc/Curation">000130</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000130</idno><idno type="wicri:Area/Pmc/Checkpoint">000599</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000599</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Discovery of Hydrocarbon-Stapled
Short α-Helical
Peptides as Promising Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) Fusion Inhibitors</title><author><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Peiyu" sort="Zhang, Peiyu" uniqKey="Zhang P" first="Peiyu" last="Zhang">Peiyu Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Tianhong" sort="Zhang, Tianhong" uniqKey="Zhang T" first="Tianhong" last="Zhang">Tianhong Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weicong" sort="Wang, Weicong" uniqKey="Wang W" first="Weicong" last="Wang">Weicong Wang</name><affiliation wicri:level="1"><nlm:aff id="aff5">Pharmaceutical Preparation Section, Plastic Surgery Hospital,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100144,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tian, Yangli" sort="Tian, Yangli" uniqKey="Tian Y" first="Yangli" last="Tian">Yangli Tian</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meng, Guangpeng" sort="Meng, Guangpeng" uniqKey="Meng G" first="Guangpeng" last="Meng">Guangpeng Meng</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Lindsley F. Kimball Research Institute,<institution>New York Blood Center</institution>, New York, New York 10065,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Keliang" sort="Liu, Keliang" uniqKey="Liu K" first="Keliang" last="Liu">Keliang Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Medicinal Chemistry</title><idno type="ISSN">0022-2623</idno><idno type="eISSN">1520-4804</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="jm7b01732_0006" id="ab-tgr1"></graphic></p><p>The hexameric α-helical coiled-coil
formed between the C-terminal
and N-terminal heptad repeat (CHR and NHR) regions of class I viral
fusion proteins plays an important role in mediating the fusion of
the viral and cellular membranes and provides a clear starting point
for molecular mimicry that drives viral fusion inhibitor design. Unfortunately,
such peptide mimicry of the short α-helical region in the CHR
of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein
has been thwarted by the loss of the peptide’s native α-helical
conformation when taken out of the parent protein structure. Here,
we describe that appropriate all-hydrocarbon stapling of the short
helical portion-based peptide to reinforce its bioactive secondary
structure remarkably improves antiviral potency. The resultant stapled
peptide P21S10 could effectively inhibit infection by MERS-CoV pseudovirus
and its spike protein-mediated cell–cell fusion; additionally,
P21S10 exhibits improved pharmacokinetic properties than HR2P-M2,
suggesting strong potential for development as an anti-MERS-CoV therapeutic.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Harrison, S C" uniqKey="Harrison S">S. C. Harrison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dimitrov, D S" uniqKey="Dimitrov D">D. S. Dimitrov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eckert, D M" uniqKey="Eckert D">D. M. Eckert</name></author><author><name sortKey="Kim, P S" uniqKey="Kim P">P. S. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vigant, F" uniqKey="Vigant F">F. Vigant</name></author><author><name sortKey="Santos, N C" uniqKey="Santos N">N. C. Santos</name></author><author><name sortKey="Lee, B" uniqKey="Lee B">B. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, M" uniqKey="Lu M">M. Lu</name></author><author><name sortKey="Blacklow, S C" uniqKey="Blacklow S">S. C. Blacklow</name></author><author><name sortKey="Kim, P S A" uniqKey="Kim P">P. S. A. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, W" uniqKey="Lai W">W. Lai</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author><author><name sortKey="Yu, F" uniqKey="Yu F">F. Yu</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X. Jiang</name></author><author><name sortKey="Xu, X" uniqKey="Xu X">X. Xu</name></author><author><name sortKey="Zhang, T" uniqKey="Zhang T">T. Zhang</name></author><author><name sortKey="Wu, S" uniqKey="Wu S">S. Wu</name></author><author><name sortKey="Zheng, X" uniqKey="Zheng X">X. Zheng</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z. Zhang</name></author><author><name sortKey="Dong, F" uniqKey="Dong F">F. Dong</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author><author><name sortKey="Liu, K" uniqKey="Liu K">K. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Follis, K E" uniqKey="Follis K">K. E. Follis</name></author><author><name sortKey="York, J" uniqKey="York J">J. York</name></author><author><name sortKey="Nunberg, J H" uniqKey="Nunberg J">J. H. Nunberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bullough, P A" uniqKey="Bullough P">P. A. Bullough</name></author><author><name sortKey="Hughson, F M" uniqKey="Hughson F">F. M. Hughson</name></author><author><name sortKey="Skehel, J J" uniqKey="Skehel J">J. J. Skehel</name></author><author><name sortKey="Wiley, D C" uniqKey="Wiley D">D. C. Wiley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, S" uniqKey="Liu S">S. Liu</name></author><author><name sortKey="Xiao, G" uniqKey="Xiao G">G. Xiao</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="He, Y X" uniqKey="He Y">Y. X. He</name></author><author><name sortKey="Niu, J K" uniqKey="Niu J">J. K. Niu</name></author><author><name sortKey="Escalante, C R" uniqKey="Escalante C">C. R. Escalante</name></author><author><name sortKey="Xiong, H" uniqKey="Xiong H">H. Xiong</name></author><author><name sortKey="Farmar, J" uniqKey="Farmar J">J. Farmar</name></author><author><name sortKey="Debnath, A K" uniqKey="Debnath A">A. K. Debnath</name></author><author><name sortKey="Tien, P" uniqKey="Tien P">P. Tien</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, E H" uniqKey="Miller E">E. H. Miller</name></author><author><name sortKey="Harrison, J S" uniqKey="Harrison J">J. S. Harrison</name></author><author><name sortKey="Radoshitzky, S R" uniqKey="Radoshitzky S">S. R. Radoshitzky</name></author><author><name sortKey="Higgins, C D" uniqKey="Higgins C">C. D. Higgins</name></author><author><name sortKey="Chi, X" uniqKey="Chi X">X. Chi</name></author><author><name sortKey="Dong, L" uniqKey="Dong L">L. Dong</name></author><author><name sortKey="Kuhn, J H" uniqKey="Kuhn J">J. H. Kuhn</name></author><author><name sortKey="Bavari, S" uniqKey="Bavari S">S. Bavari</name></author><author><name sortKey="Lai, J" uniqKey="Lai J">J. Lai</name></author><author><name sortKey="Chandran, K" uniqKey="Chandran K">K. Chandran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y. Zhu</name></author><author><name sortKey="Chan, K" uniqKey="Chan K">K. Chan</name></author><author><name sortKey="Qin, L" uniqKey="Qin L">L. Qin</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Chan, J F" uniqKey="Chan J">J. F. Chan</name></author><author><name sortKey="Du, L" uniqKey="Du L">L. Du</name></author><author><name sortKey="Yu, F" uniqKey="Yu F">F. Yu</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C. Ma</name></author><author><name sortKey="Ye, S" uniqKey="Ye S">S. Ye</name></author><author><name sortKey="Yuen, K" uniqKey="Yuen K">K. Yuen</name></author><author><name sortKey="Zhang, R" uniqKey="Zhang R">R. Zhang</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berkhout, B" uniqKey="Berkhout B">B. Berkhout</name></author><author><name sortKey="Eggink, D" uniqKey="Eggink D">D. Eggink</name></author><author><name sortKey="Sanders, R W" uniqKey="Sanders R">R. W. Sanders</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azzarito, V" uniqKey="Azzarito V">V. Azzarito</name></author><author><name sortKey="Long, K" uniqKey="Long K">K. Long</name></author><author><name sortKey="Murphy, N S" uniqKey="Murphy N">N. S. Murphy</name></author><author><name sortKey="Wilson, A J" uniqKey="Wilson A">A. J. Wilson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, L" uniqKey="Cai L">L. Cai</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, C" uniqKey="Pan C">C. Pan</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S. Liu</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, J" uniqKey="Gao J">J. Gao</name></author><author><name sortKey="Lu, G" uniqKey="Lu G">G. Lu</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J. Qi</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y. Wu</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y. Deng</name></author><author><name sortKey="Geng, H" uniqKey="Geng H">H. Geng</name></author><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Xiao, H" uniqKey="Xiao H">H. Xiao</name></author><author><name sortKey="Tan, W" uniqKey="Tan W">W. Tan</name></author><author><name sortKey="Yan, J" uniqKey="Yan J">J. Yan</name></author><author><name sortKey="Gao, G" uniqKey="Gao G">G. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Y" uniqKey="Lau Y">Y. Lau</name></author><author><name sortKey="De Andrade, P" uniqKey="De Andrade P">P. De Andrade</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y. Wu</name></author><author><name sortKey="Spring, D R" uniqKey="Spring D">D. R. Spring</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walensky, L D" uniqKey="Walensky L">L. D. Walensky</name></author><author><name sortKey="Bird, G H" uniqKey="Bird G">G. H. Bird</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Y" uniqKey="Tan Y">Y. Tan</name></author><author><name sortKey="Lane, D P" uniqKey="Lane D">D. P. Lane</name></author><author><name sortKey="Verma, C S" uniqKey="Verma C">C. S. Verma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawamoto, S A" uniqKey="Kawamoto S">S. A. Kawamoto</name></author><author><name sortKey="Coleska, A" uniqKey="Coleska A">A. Coleska</name></author><author><name sortKey="Ran, X" uniqKey="Ran X">X. Ran</name></author><author><name sortKey="Yi, H" uniqKey="Yi H">H. Yi</name></author><author><name sortKey="Yang, C" uniqKey="Yang C">C. Yang</name></author><author><name sortKey="Wang, S" uniqKey="Wang S">S. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hojo, K" uniqKey="Hojo K">K. Hojo</name></author><author><name sortKey="Hossain, M A" uniqKey="Hossain M">M. A. Hossain</name></author><author><name sortKey="Tailhades, J" uniqKey="Tailhades J">J. Tailhades</name></author><author><name sortKey="Shabanpoor, F" uniqKey="Shabanpoor F">F. Shabanpoor</name></author><author><name sortKey="Wong, L L L" uniqKey="Wong L">L. L.L. Wong</name></author><author><name sortKey="Ong Palsson, E E K" uniqKey="Ong Palsson E">E. E. K. Ong-Palsson</name></author><author><name sortKey="Kastman, H E" uniqKey="Kastman H">H. E. Kastman</name></author><author><name sortKey="Ma, S" uniqKey="Ma S">S. Ma</name></author><author><name sortKey="Gundlach, A L" uniqKey="Gundlach A">A. L. Gundlach</name></author><author><name sortKey="Rosengren, K J" uniqKey="Rosengren K">K. J. Rosengren</name></author><author><name sortKey="Wade, J D" uniqKey="Wade J">J. D. Wade</name></author><author><name sortKey="Bathgate, R A D" uniqKey="Bathgate R">R. A. D. Bathgate</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frank, A O" uniqKey="Frank A">A. O. Frank</name></author><author><name sortKey="Vangamudi, B" uniqKey="Vangamudi B">B. Vangamudi</name></author><author><name sortKey="Feldkamp, M D" uniqKey="Feldkamp M">M. D. Feldkamp</name></author><author><name sortKey="Souza Fagundes, E M" uniqKey="Souza Fagundes E">E. M. Souza-Fagundes</name></author><author><name sortKey="Luzwick, J W" uniqKey="Luzwick J">J. W. Luzwick</name></author><author><name sortKey="Cortez, D" uniqKey="Cortez D">D. Cortez</name></author><author><name sortKey="Olejniczak, E T" uniqKey="Olejniczak E">E. T. Olejniczak</name></author><author><name sortKey="Waterson, A G" uniqKey="Waterson A">A. G. Waterson</name></author><author><name sortKey="Rossanese, O W" uniqKey="Rossanese O">O. W. Rossanese</name></author><author><name sortKey="Chazin, W J" uniqKey="Chazin W">W. J. Chazin</name></author><author><name sortKey="Fesik, S W" uniqKey="Fesik S">S. W. Fesik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hilinski, G J" uniqKey="Hilinski G">G. J. Hilinski</name></author><author><name sortKey="Kim, Y W" uniqKey="Kim Y">Y. W. Kim</name></author><author><name sortKey="Hong, J" uniqKey="Hong J">J. Hong</name></author><author><name sortKey="Kutchukian, P S" uniqKey="Kutchukian P">P. S. Kutchukian</name></author><author><name sortKey="Crenshaw, C M" uniqKey="Crenshaw C">C. M. Crenshaw</name></author><author><name sortKey="Berkovitch, S S" uniqKey="Berkovitch S">S. S. Berkovitch</name></author><author><name sortKey="Chang, A" uniqKey="Chang A">A. Chang</name></author><author><name sortKey="Ham, S" uniqKey="Ham S">S. Ham</name></author><author><name sortKey="Verdine, G L" uniqKey="Verdine G">G. L. Verdine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Y" uniqKey="Chang Y">Y. Chang</name></author><author><name sortKey="Graves, B" uniqKey="Graves B">B. Graves</name></author><author><name sortKey="Guerlavais, V" uniqKey="Guerlavais V">V. Guerlavais</name></author><author><name sortKey="Tovar, C" uniqKey="Tovar C">C. Tovar</name></author><author><name sortKey="Packman, K" uniqKey="Packman K">K. Packman</name></author><author><name sortKey="To, K H" uniqKey="To K">K. H. To</name></author><author><name sortKey="Olson, K A" uniqKey="Olson K">K. A. Olson</name></author><author><name sortKey="Kesavan, K" uniqKey="Kesavan K">K. Kesavan</name></author><author><name sortKey="Gangurde, P" uniqKey="Gangurde P">P. Gangurde</name></author><author><name sortKey="Mukherjee, A" uniqKey="Mukherjee A">A. Mukherjee</name></author><author><name sortKey="Baker, T" uniqKey="Baker T">T. Baker</name></author><author><name sortKey="Darlak, K" uniqKey="Darlak K">K. Darlak</name></author><author><name sortKey="Elkin, C" uniqKey="Elkin C">C. Elkin</name></author><author><name sortKey="Filipovic, Z" uniqKey="Filipovic Z">Z. Filipovic</name></author><author><name sortKey="Qureshi, F Z" uniqKey="Qureshi F">F. Z. Qureshi</name></author><author><name sortKey="Cai, H" uniqKey="Cai H">H. Cai</name></author><author><name sortKey="Berry, P" uniqKey="Berry P">P. Berry</name></author><author><name sortKey="Feyfant, E" uniqKey="Feyfant E">E. Feyfant</name></author><author><name sortKey="Shi, X E" uniqKey="Shi X">X. E. Shi</name></author><author><name sortKey="Horstick, J" uniqKey="Horstick J">J. Horstick</name></author><author><name sortKey="Annis, D A" uniqKey="Annis D">D. A. Annis</name></author><author><name sortKey="Manning, A M" uniqKey="Manning A">A. M. Manning</name></author><author><name sortKey="Fotouhi, N" uniqKey="Fotouhi N">N. Fotouhi</name></author><author><name sortKey="Nash, H" uniqKey="Nash H">H. Nash</name></author><author><name sortKey="Vassilev, L T" uniqKey="Vassilev L">L. T. Vassilev</name></author><author><name sortKey="Sawyer, T K" uniqKey="Sawyer T">T. K. Sawyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name></author><author><name sortKey="Cai, L" uniqKey="Cai L">L. Cai</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Zhang, T" uniqKey="Zhang T">T. Zhang</name></author><author><name sortKey="Li, J" uniqKey="Li J">J. Li</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z. Zhang</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K. Wang</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L. Xu</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X. Jiang</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author><author><name sortKey="Liu, K" uniqKey="Liu K">K. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name></author><author><name sortKey="Cai, L" uniqKey="Cai L">L. Cai</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Yu, F" uniqKey="Yu F">F. Yu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X. Jiang</name></author><author><name sortKey="Xu, X" uniqKey="Xu X">X. Xu</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K. Wang</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L. Xu</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author><author><name sortKey="Liu, K" uniqKey="Liu K">K. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wuo, M" uniqKey="Wuo M">M. Wuo</name></author><author><name sortKey="Mahon, A B" uniqKey="Mahon A">A. B. Mahon</name></author><author><name sortKey="Arora, P S" uniqKey="Arora P">P. S. Arora</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Apostolovic, B" uniqKey="Apostolovic B">B. Apostolovic</name></author><author><name sortKey="Danial, M" uniqKey="Danial M">M. Danial</name></author><author><name sortKey="Klok, H A" uniqKey="Klok H">H. A. Klok</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zheng, B" uniqKey="Zheng B">B. Zheng</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K. Wang</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Yu, F" uniqKey="Yu F">F. Yu</name></author><author><name sortKey="Cheng, M" uniqKey="Cheng M">M. Cheng</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author><author><name sortKey="Liu, K" uniqKey="Liu K">K. Liu</name></author><author><name sortKey="Cai, L" uniqKey="Cai L">L. Cai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qi, Z" uniqKey="Qi Z">Z. Qi</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name></author><author><name sortKey="Xue, N" uniqKey="Xue N">N. Xue</name></author><author><name sortKey="Pan, C" uniqKey="Pan C">C. Pan</name></author><author><name sortKey="Jing, W" uniqKey="Jing W">W. Jing</name></author><author><name sortKey="Liu, K" uniqKey="Liu K">K. Liu</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anderhuber, N" uniqKey="Anderhuber N">N. Anderhuber</name></author><author><name sortKey="Fladischer, P" uniqKey="Fladischer P">P. Fladischer</name></author><author><name sortKey="Gruber Khadjawi, M" uniqKey="Gruber Khadjawi M">M. Gruber-Khadjawi</name></author><author><name sortKey="Mairhofer, J" uniqKey="Mairhofer J">J. Mairhofer</name></author><author><name sortKey="Striedner, G" uniqKey="Striedner G">G. Striedner</name></author><author><name sortKey="Wiltschi, B" uniqKey="Wiltschi B">B. Wiltschi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fletcher, J M" uniqKey="Fletcher J">J. M. Fletcher</name></author><author><name sortKey="Boyle, A L" uniqKey="Boyle A">A. L. Boyle</name></author><author><name sortKey="Bruning, M" uniqKey="Bruning M">M. Bruning</name></author><author><name sortKey="Bartlett, G J" uniqKey="Bartlett G">G. J. Bartlett</name></author><author><name sortKey="Vincent, T L" uniqKey="Vincent T">T. L. Vincent</name></author><author><name sortKey="Zaccai, N R" uniqKey="Zaccai N">N. R. Zaccai</name></author><author><name sortKey="Armstrong, C T" uniqKey="Armstrong C">C. T. Armstrong</name></author><author><name sortKey="Bromley, E H C" uniqKey="Bromley E">E. H. C. Bromley</name></author><author><name sortKey="Booth, P J" uniqKey="Booth P">P. J. Booth</name></author><author><name sortKey="Brady, R L" uniqKey="Brady R">R. L. Brady</name></author><author><name sortKey="Thomson, A R" uniqKey="Thomson A">A. R. Thomson</name></author><author><name sortKey="Woolfson, D N" uniqKey="Woolfson D">D. N. Woolfson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cotten, M" uniqKey="Cotten M">M. Cotten</name></author><author><name sortKey="Watson, S J" uniqKey="Watson S">S. J. Watson</name></author><author><name sortKey="Zumla, A I" uniqKey="Zumla A">A. I. Zumla</name></author><author><name sortKey="Makhdoom, H Q" uniqKey="Makhdoom H">H. Q. Makhdoom</name></author><author><name sortKey="Palser, A L" uniqKey="Palser A">A. L. Palser</name></author><author><name sortKey="Ong, S H" uniqKey="Ong S">S. H. Ong</name></author><author><name sortKey="Al Rabeeah, A A" uniqKey="Al Rabeeah A">A. A. Al Rabeeah</name></author><author><name sortKey="Alhakeem, R F" uniqKey="Alhakeem R">R. F. Alhakeem</name></author><author><name sortKey="Assiri, A" uniqKey="Assiri A">A. Assiri</name></author><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J. A. Al-Tawfiq</name></author><author><name sortKey="Albarrak, A" uniqKey="Albarrak A">A. Albarrak</name></author><author><name sortKey="Barry, M" uniqKey="Barry M">M. Barry</name></author><author><name sortKey="Shibl, A" uniqKey="Shibl A">A. Shibl</name></author><author><name sortKey="Alrabiah, F A" uniqKey="Alrabiah F">F. A. Alrabiah</name></author><author><name sortKey="Hajjar, S" uniqKey="Hajjar S">S. Hajjar</name></author><author><name sortKey="Balkhy, H H" uniqKey="Balkhy H">H. H. Balkhy</name></author><author><name sortKey="Flemban, H" uniqKey="Flemban H">H. Flemban</name></author><author><name sortKey="Rambaut, A" uniqKey="Rambaut A">A. Rambaut</name></author><author><name sortKey="Kellam, P" uniqKey="Kellam P">P. Kellam</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lawless, M K" uniqKey="Lawless M">M. K. Lawless</name></author><author><name sortKey="Barney, S" uniqKey="Barney S">S. Barney</name></author><author><name sortKey="Guthrie, K I" uniqKey="Guthrie K">K. I. Guthrie</name></author><author><name sortKey="Bucy, T B" uniqKey="Bucy T">T. B. Bucy</name></author><author><name sortKey="Petteway, S R" uniqKey="Petteway S">S. R. Petteway</name></author><author><name sortKey="Merutka, G" uniqKey="Merutka G">G. Merutka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, L F" uniqKey="Cai L">L. F. Cai</name></author><author><name sortKey="Balogh, E" uniqKey="Balogh E">E. Balogh</name></author><author><name sortKey="Gochin, M" uniqKey="Gochin M">M. Gochin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dwyer, J J" uniqKey="Dwyer J">J. J. Dwyer</name></author><author><name sortKey="Wilson, K L" uniqKey="Wilson K">K. L. Wilson</name></author><author><name sortKey="Davison, D K" uniqKey="Davison D">D. K. Davison</name></author><author><name sortKey="Freel, S A" uniqKey="Freel S">S. A. Freel</name></author><author><name sortKey="Seedorff, J E" uniqKey="Seedorff J">J. E. Seedorff</name></author><author><name sortKey="Wring, S A" uniqKey="Wring S">S. A. Wring</name></author><author><name sortKey="Tvermoes, N A" uniqKey="Tvermoes N">N. A. Tvermoes</name></author><author><name sortKey="Matthews, T J" uniqKey="Matthews T">T. J. Matthews</name></author><author><name sortKey="Greenberg, M L" uniqKey="Greenberg M">M. L. Greenberg</name></author><author><name sortKey="Delmedico, M K" uniqKey="Delmedico M">M. K. Delmedico</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, W G" uniqKey="Shi W">W. G. Shi</name></author><author><name sortKey="Cai, L F" uniqKey="Cai L">L. F. Cai</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K. Wang</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L. Xu</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S. Zhang</name></author><author><name sortKey="Han, H" uniqKey="Han H">H. Han</name></author><author><name sortKey="Jiang, X F" uniqKey="Jiang X">X. F. Jiang</name></author><author><name sortKey="Zheng, B H" uniqKey="Zheng B">B. H. Zheng</name></author><author><name sortKey="Jiang, S B" uniqKey="Jiang S">S. B. Jiang</name></author><author><name sortKey="Liu, K L" uniqKey="Liu K">K. L. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, X J" uniqKey="Zhu X">X. J. Zhu</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y. Zhu</name></author><author><name sortKey="Ye, S" uniqKey="Ye S">S. Ye</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Xu, W" uniqKey="Xu W">W. Xu</name></author><author><name sortKey="Su, S" uniqKey="Su S">S. Su</name></author><author><name sortKey="Sun, Z W" uniqKey="Sun Z">Z. W. Sun</name></author><author><name sortKey="Yu, F" uniqKey="Yu F">F. Yu</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author><author><name sortKey="Zhang, T H" uniqKey="Zhang T">T. H. Zhang</name></author><author><name sortKey="Zhang, Z Q" uniqKey="Zhang Z">Z. Q. Zhang</name></author><author><name sortKey="Zhang, X Y" uniqKey="Zhang X">X. Y. Zhang</name></author><author><name sortKey="Xu, J Q" uniqKey="Xu J">J. Q. Xu</name></author><author><name sortKey="Du, L Y" uniqKey="Du L">L. Y. Du</name></author><author><name sortKey="Liu, K L" uniqKey="Liu K">K. L. Liu</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Zhang, R G" uniqKey="Zhang R">R. G. Zhang</name></author><author><name sortKey="Jiang, S B" uniqKey="Jiang S">S. B. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cui, H" uniqKey="Cui H">H. Cui</name></author><author><name sortKey="Qing, J" uniqKey="Qing J">J. Qing</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y. Guo</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Cui, L" uniqKey="Cui L">L. Cui</name></author><author><name sortKey="He, T" uniqKey="He T">T. He</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Liu, L" uniqKey="Liu L">L. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Xia, S" uniqKey="Xia S">S. Xia</name></author><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Du, L" uniqKey="Du L">L. Du</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xia, S" uniqKey="Xia S">S. Xia</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author><author><name sortKey="Su, S" uniqKey="Su S">S. Su</name></author><author><name sortKey="Du, L" uniqKey="Du L">L. Du</name></author><author><name sortKey="Ying, T" uniqKey="Ying T">T. Ying</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, G" uniqKey="Zhao G">G. Zhao</name></author><author><name sortKey="Du, L" uniqKey="Du L">L. Du</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C. Ma</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Li, L" uniqKey="Li L">L. Li</name></author><author><name sortKey="Poon, V K" uniqKey="Poon V">V. K. Poon</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Yu, F" uniqKey="Yu F">F. Yu</name></author><author><name sortKey="Zheng, B J" uniqKey="Zheng B">B. J. Zheng</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y. Zhou</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Med Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Med. Chem</journal-id><journal-id journal-id-type="publisher-id">jm</journal-id><journal-id journal-id-type="coden">jmcmar</journal-id><journal-title-group><journal-title>Journal of Medicinal Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0022-2623</issn><issn pub-type="epub">1520-4804</issn><publisher><publisher-name>American Chemical
Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29442512</article-id><article-id pub-id-type="pmc">7075646</article-id><article-id pub-id-type="doi">10.1021/acs.jmedchem.7b01732</article-id><article-categories><subj-group><subject>Article</subject></subj-group></article-categories><title-group><article-title>Discovery of Hydrocarbon-Stapled
Short α-Helical
Peptides as Promising Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) Fusion Inhibitors</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Wang</surname><given-names>Chao</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="notes3" ref-type="notes">¶</xref></contrib><contrib contrib-type="author" id="ath2"><name><surname>Xia</surname><given-names>Shuai</given-names></name><xref rid="aff2" ref-type="aff">‡</xref><xref rid="notes3" ref-type="notes">¶</xref></contrib><contrib contrib-type="author" id="ath3"><name><surname>Zhang</surname><given-names>Peiyu</given-names></name><xref rid="aff3" ref-type="aff">§</xref><xref rid="notes3" ref-type="notes">¶</xref></contrib><contrib contrib-type="author" id="ath4"><name><surname>Zhang</surname><given-names>Tianhong</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath5"><name><surname>Wang</surname><given-names>Weicong</given-names></name><xref rid="aff5" ref-type="aff">⊥</xref></contrib><contrib contrib-type="author" id="ath6"><name><surname>Tian</surname><given-names>Yangli</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath7"><name><surname>Meng</surname><given-names>Guangpeng</given-names></name><xref rid="aff3" ref-type="aff">§</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath8"><name><surname>Jiang</surname><given-names>Shibo</given-names></name><xref rid="cor2" ref-type="other">*</xref><xref rid="aff2" ref-type="aff">‡</xref><xref rid="aff4" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath9"><name><surname>Liu</surname><given-names>Keliang</given-names></name><xref rid="cor1" ref-type="other">*</xref><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff3" ref-type="aff">§</xref></contrib><aff id="aff1"><label>†</label>State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></aff><aff id="aff2"><label>‡</label>Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></aff><aff id="aff3"><label>§</label>Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></aff><aff id="aff4"><label>∥</label>Lindsley F. Kimball Research Institute,<institution>New York Blood Center</institution>, New York, New York 10065,<country>United States</country></aff><aff id="aff5"><label>⊥</label>Pharmaceutical Preparation Section, Plastic Surgery Hospital,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100144,<country>China</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>For K.L.: phone, <phone>86-10-6816-9363</phone>; fax, <fax>86-10-6821-1656</fax>; E-mail, <email>keliangliu55@126.com</email>.</corresp><corresp id="cor2"><label>*</label>For S.J.: phone, <phone>86-21-54237673</phone>; fax, <fax>86-21-54237465</fax>; E-mail, <email>shibojiang@fudan.edu.cn</email>.</corresp></author-notes><pub-date pub-type="epub"><day>14</day><month>02</month><year>2018</year></pub-date><pub-date pub-type="ppub"><day>08</day><month>03</month><year>2018</year></pub-date><volume>61</volume><issue>5</issue><fpage>2018</fpage><lpage>2026</lpage><history><date date-type="received"><day>22</day><month>11</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2018 American Chemical
Society</copyright-statement><copyright-year>2018</copyright-year><copyright-holder>American Chemical
Society</copyright-holder><license license-type="open-access"><license-p>This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="jm7b01732_0006" id="ab-tgr1"></graphic></p><p>The hexameric α-helical coiled-coil
formed between the C-terminal
and N-terminal heptad repeat (CHR and NHR) regions of class I viral
fusion proteins plays an important role in mediating the fusion of
the viral and cellular membranes and provides a clear starting point
for molecular mimicry that drives viral fusion inhibitor design. Unfortunately,
such peptide mimicry of the short α-helical region in the CHR
of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein
has been thwarted by the loss of the peptide’s native α-helical
conformation when taken out of the parent protein structure. Here,
we describe that appropriate all-hydrocarbon stapling of the short
helical portion-based peptide to reinforce its bioactive secondary
structure remarkably improves antiviral potency. The resultant stapled
peptide P21S10 could effectively inhibit infection by MERS-CoV pseudovirus
and its spike protein-mediated cell–cell fusion; additionally,
P21S10 exhibits improved pharmacokinetic properties than HR2P-M2,
suggesting strong potential for development as an anti-MERS-CoV therapeutic.</p></abstract><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>jm7b01732</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>jm7b01732</meta-value></custom-meta><custom-meta><meta-name>ccc-price</meta-name><meta-value></meta-value></custom-meta></custom-meta-group></article-meta><notes id="notes-d1e21-autogenerated"><fn-group><fn fn-type="" id="d30e234"><p>This article is made available for a limited time sponsored by ACS under the <ext-link ext-link-type="uri" xlink:href="http://pubs.acs.org/page/policy/freetoread/index.html">ACS Free to Read License</ext-link>, which permits copying and redistribution of the article for non-commercial scholarly purposes.</p></fn></fn-group></notes></front></pmc><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name></noRegion><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><name sortKey="Liu, Keliang" sort="Liu, Keliang" uniqKey="Liu K" first="Keliang" last="Liu">Keliang Liu</name><name sortKey="Liu, Keliang" sort="Liu, Keliang" uniqKey="Liu K" first="Keliang" last="Liu">Keliang Liu</name><name sortKey="Meng, Guangpeng" sort="Meng, Guangpeng" uniqKey="Meng G" first="Guangpeng" last="Meng">Guangpeng Meng</name><name sortKey="Tian, Yangli" sort="Tian, Yangli" uniqKey="Tian Y" first="Yangli" last="Tian">Yangli Tian</name><name sortKey="Wang, Weicong" sort="Wang, Weicong" uniqKey="Wang W" first="Weicong" last="Wang">Weicong Wang</name><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><name sortKey="Zhang, Peiyu" sort="Zhang, Peiyu" uniqKey="Zhang P" first="Peiyu" last="Zhang">Peiyu Zhang</name><name sortKey="Zhang, Tianhong" sort="Zhang, Tianhong" uniqKey="Zhang T" first="Tianhong" last="Zhang">Tianhong Zhang</name></country><country name="États-Unis"><noRegion><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000599 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 000599 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Pmc
|étape= Checkpoint
|type= RBID
|clé= PMC:7075646
|texte= Discovery of Hydrocarbon-Stapled
Short α-Helical
Peptides as Promising Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) Fusion Inhibitors
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:29442512" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |