Structure-Based Stabilization of Non-native Protein–Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design
Identifieur interne : 000133 ( Pmc/Curation ); précédent : 000132; suivant : 000134Structure-Based Stabilization of Non-native Protein–Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design
Auteurs : Shan-Meng Lin [Taïwan] ; Shih-Chao Lin [États-Unis] ; Jia-Ning Hsu [Taïwan] ; Chung-Ke Chang [Taïwan] ; Ching-Ming Chien [Taïwan] ; Yong-Sheng Wang [Taïwan] ; Hung-Yi Wu [Taïwan] ; U-Ser Jeng [Taïwan] ; Kylene Kehn-Hall [États-Unis] ; Ming-Hon Hou [Taïwan]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2020.
Abstract
Structure-based stabilization of protein–protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs, and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases.
Url:
DOI: 10.1021/acs.jmedchem.9b01913
PubMed: 32105468
PubMed Central: 7094172
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Stabilization of Non-native Protein–Protein
Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug
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Kylene" sort="Kehn Hall, Kylene" uniqKey="Kehn Hall K" first="Kylene" last="Kehn-Hall">Kylene Kehn-Hall</name><affiliation wicri:level="1"><nlm:aff id="aff3">National Center for Biodefense and Infectious Diseases, School of Systems Biology,<institution>George Mason University</institution>, Manassas, Virginia 20110,<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="Hou, Ming Hon" sort="Hou, Ming Hon" uniqKey="Hou M" first="Ming-Hon" last="Hou">Ming-Hon Hou</name><affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Genomics and Bioinformatics,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32105468</idno><idno type="pmc">7094172</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094172</idno><idno type="RBID">PMC:7094172</idno><idno type="doi">10.1021/acs.jmedchem.9b01913</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000133</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000133</idno><idno type="wicri:Area/Pmc/Curation">000133</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000133</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structure-Based
Stabilization of Non-native Protein–Protein
Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug
Design</title><author><name sortKey="Lin, Shan Meng" sort="Lin, Shan Meng" uniqKey="Lin S" first="Shan-Meng" last="Lin">Shan-Meng Lin</name><affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Genomics and Bioinformatics,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lin, Shih Chao" sort="Lin, Shih Chao" uniqKey="Lin S" first="Shih-Chao" last="Lin">Shih-Chao Lin</name><affiliation wicri:level="1"><nlm:aff id="aff3">National Center for Biodefense and Infectious Diseases, School of Systems Biology,<institution>George Mason University</institution>, Manassas, Virginia 20110,<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="Hsu, Jia Ning" sort="Hsu, Jia Ning" uniqKey="Hsu J" first="Jia-Ning" last="Hsu">Jia-Ning Hsu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Genomics and Bioinformatics,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Chung Ke" sort="Chang, Chung Ke" uniqKey="Chang C" first="Chung-Ke" last="Chang">Chung-Ke Chang</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Institute of Biomedical Sciences, Academia Sinica</institution>, Taipei 115,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chien, Ching Ming" sort="Chien, Ching Ming" uniqKey="Chien C" first="Ching-Ming" last="Chien">Ching-Ming Chien</name><affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Genomics and Bioinformatics,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yong Sheng" sort="Wang, Yong Sheng" uniqKey="Wang Y" first="Yong-Sheng" last="Wang">Yong-Sheng Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Genomics and Bioinformatics,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wu, Hung Yi" sort="Wu, Hung Yi" uniqKey="Wu H" first="Hung-Yi" last="Wu">Hung-Yi Wu</name><affiliation wicri:level="1"><nlm:aff id="aff4">Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine,<institution>National Chung Hsing University</institution>, Taichung 40227,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jeng, U Ser" sort="Jeng, U Ser" uniqKey="Jeng U" first="U-Ser" last="Jeng">U-Ser Jeng</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>National Synchrotron Radiation Research Center</institution>, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu 30076,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Chemical Engineering,<institution>National Tsing Hua University</institution>, Hsinchu 30013,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kehn Hall, Kylene" sort="Kehn Hall, Kylene" uniqKey="Kehn Hall K" first="Kylene" last="Kehn-Hall">Kylene Kehn-Hall</name><affiliation wicri:level="1"><nlm:aff id="aff3">National Center for Biodefense and Infectious Diseases, School of Systems Biology,<institution>George Mason University</institution>, Manassas, Virginia 20110,<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="Hou, Ming Hon" sort="Hou, Ming Hon" uniqKey="Hou M" first="Ming-Hon" last="Hou">Ming-Hon Hou</name><affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Genomics and Bioinformatics,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></nlm:aff><country xml:lang="fr">Taïwan</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="2020">2020</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="jm9b01913_0005" id="ab-tgr1"></graphic></p><p>Structure-based
stabilization of protein–protein interactions
(PPIs) is a promising strategy for drug discovery. However, this approach
has mainly focused on the stabilization of native PPIs, and non-native
PPIs have received little consideration. Here, we identified a non-native
interaction interface on the three-dimensional dimeric structure of
the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV
N-NTD). The interface formed a conserved hydrophobic cavity suitable
for targeted drug screening. By considering the hydrophobic
complementarity during the virtual screening step, we identified 5-benzyloxygramine
as a new N protein PPI orthosteric stabilizer that exhibits both antiviral
and N-NTD protein-stabilizing activities. X-ray crystallography and
small-angle
X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD
dimers through simultaneous hydrophobic interactions with both partners,
resulting in abnormal N protein oligomerization that was further confirmed
in the cell. This unique approach based on the identification and
stabilization of non-native PPIs of N protein could be applied toward
drug discovery against CoV diseases.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bosch, J" uniqKey="Bosch J">J. Bosch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sijbesma, E" uniqKey="Sijbesma E">E. Sijbesma</name></author><author><name sortKey="Hallenbeck, K K" uniqKey="Hallenbeck K">K. K. Hallenbeck</name></author><author><name sortKey="Leysen, S" uniqKey="Leysen S">S. Leysen</name></author><author><name sortKey="De Vink, P J" uniqKey="De Vink P">P. J. de Vink</name></author><author><name sortKey="Sk Ra, L" uniqKey="Sk Ra L">L. Skóra</name></author><author><name sortKey="Jahnke, W" uniqKey="Jahnke W">W. Jahnke</name></author><author><name sortKey="Brunsveld, L" uniqKey="Brunsveld L">L. Brunsveld</name></author><author><name sortKey="Arkin, M R" uniqKey="Arkin M">M. R. Arkin</name></author><author><name sortKey="Ottmann, C" uniqKey="Ottmann C">C. Ottmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stevers, L M" uniqKey="Stevers L">L. M. Stevers</name></author><author><name sortKey="Sijbesma, E" uniqKey="Sijbesma E">E. Sijbesma</name></author><author><name sortKey="Botta, M" uniqKey="Botta M">M. Botta</name></author><author><name sortKey="Mackintosh, C" uniqKey="Mackintosh C">C. MacKintosh</name></author><author><name sortKey="Obsil, T" uniqKey="Obsil T">T. Obsil</name></author><author><name sortKey="Landrieu, I" uniqKey="Landrieu I">I. Landrieu</name></author><author><name sortKey="Cau, Y" uniqKey="Cau Y">Y. Cau</name></author><author><name sortKey="Wilson, A J" uniqKey="Wilson A">A. J. Wilson</name></author><author><name sortKey="Karawajczyk, A" uniqKey="Karawajczyk A">A. Karawajczyk</name></author><author><name sortKey="Eickhoff, J" uniqKey="Eickhoff J">J. Eickhoff</name></author><author><name sortKey="Davis, J" uniqKey="Davis J">J. Davis</name></author><author><name sortKey="Hann, M" uniqKey="Hann M">M. Hann</name></author><author><name sortKey="O Ahony, G" uniqKey="O Ahony G">G. O’Mahony</name></author><author><name sortKey="Doveston, R G" uniqKey="Doveston R">R. G. Doveston</name></author><author><name sortKey="Brunsveld, L" uniqKey="Brunsveld L">L. Brunsveld</name></author><author><name sortKey="Ottmann, C" uniqKey="Ottmann C">C. Ottmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ni, D" uniqKey="Ni D">D. Ni</name></author><author><name sortKey="Lu, S" uniqKey="Lu S">S. Lu</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fischer, G" uniqKey="Fischer G">G. Fischer</name></author><author><name sortKey="Rossmann, M" uniqKey="Rossmann M">M. Rossmann</name></author><author><name sortKey="Hyvonen, M" uniqKey="Hyvonen M">M. Hyvonen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Petta, I" uniqKey="Petta I">I. Petta</name></author><author><name sortKey="Lievens, S" uniqKey="Lievens S">S. Lievens</name></author><author><name sortKey="Libert, C" uniqKey="Libert C">C. Libert</name></author><author><name sortKey="Tavernier, J" uniqKey="Tavernier J">J. Tavernier</name></author><author><name sortKey="De Bosscher, K" uniqKey="De Bosscher K">K. De Bosscher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhong, M" uniqKey="Zhong M">M. Zhong</name></author><author><name sortKey="Lee, G M" uniqKey="Lee G">G. M. Lee</name></author><author><name sortKey="Sijbesma, E" uniqKey="Sijbesma E">E. Sijbesma</name></author><author><name sortKey="Ottmann, C" uniqKey="Ottmann C">C. Ottmann</name></author><author><name sortKey="Arkin, M R" uniqKey="Arkin M">M. R. Arkin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, C H" uniqKey="Yang C">C. H. Yang</name></author><author><name sortKey="Horwitz, S B" uniqKey="Horwitz S">S. B. Horwitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yuan, Y" uniqKey="Yuan Y">Y. Yuan</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Du, W" uniqKey="Du W">W. Du</name></author><author><name sortKey="Ding, Z" uniqKey="Ding Z">Z. Ding</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Han, T" uniqKey="Han T">T. Han</name></author><author><name sortKey="An, L" uniqKey="An L">L. An</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name></author><author><name sortKey="Liang, G" uniqKey="Liang G">G. Liang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saxton, R A" uniqKey="Saxton R">R. A. Saxton</name></author><author><name sortKey="Sabatini, D M" uniqKey="Sabatini D">D. M. Sabatini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="White, K M" uniqKey="White K">K. M. White</name></author><author><name sortKey="Abreu, P" uniqKey="Abreu P">P. Abreu</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author><author><name sortKey="De Jesus, P D" uniqKey="De Jesus P">P. D. De Jesus</name></author><author><name sortKey="Manicassamy, B" uniqKey="Manicassamy B">B. Manicassamy</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. García-Sastre</name></author><author><name sortKey="Chanda, S K" uniqKey="Chanda S">S. K. Chanda</name></author><author><name sortKey="Devita, R J" uniqKey="Devita R">R. J. DeVita</name></author><author><name sortKey="Shaw, M L" uniqKey="Shaw M">M. L. Shaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A. M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T. M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A. D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Forni, D" uniqKey="Forni D">D. Forni</name></author><author><name sortKey="Cagliani, R" uniqKey="Cagliani R">R. Cagliani</name></author><author><name sortKey="Clerici, M" uniqKey="Clerici M">M. Clerici</name></author><author><name sortKey="Sironi, M" uniqKey="Sironi M">M. Sironi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mubarak, A" uniqKey="Mubarak A">A. Mubarak</name></author><author><name sortKey="Alturaiki, W" uniqKey="Alturaiki W">W. Alturaiki</name></author><author><name sortKey="Hemida, M G" uniqKey="Hemida M">M. G. Hemida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, N" uniqKey="Zhu N">N. Zhu</name></author><author><name sortKey="Zhang, D" uniqKey="Zhang D">D. Zhang</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W. Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Yang, B" uniqKey="Yang B">B. Yang</name></author><author><name sortKey="Song, J" uniqKey="Song J">J. Song</name></author><author><name sortKey="Zhao, X" uniqKey="Zhao X">X. Zhao</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B. Huang</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name></author><author><name sortKey="Lu, R" uniqKey="Lu R">R. Lu</name></author><author><name sortKey="Niu, P" uniqKey="Niu P">P. Niu</name></author><author><name sortKey="Zhan, F" uniqKey="Zhan F">F. Zhan</name></author><author><name sortKey="Ma, X" uniqKey="Ma X">X. Ma</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D. Wang</name></author><author><name sortKey="Xu, W" uniqKey="Xu W">W. Xu</name></author><author><name sortKey="Wu, G" uniqKey="Wu G">G. Wu</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G. F. Gao</name></author><author><name sortKey="Tan, W" uniqKey="Tan W">W. Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author><author><name sortKey="E, I X0a A" uniqKey="E I">I.
A. E</name></author><author><name sortKey="Madani, T A" uniqKey="Madani T">T. A. Madani</name></author><author><name sortKey="Ntoumi, F" uniqKey="Ntoumi F">F. Ntoumi</name></author><author><name sortKey="Kock, R" uniqKey="Kock R">R. Kock</name></author><author><name sortKey="Dar, O" uniqKey="Dar O">O. Dar</name></author><author><name sortKey="Ippolito, G" uniqKey="Ippolito G">G. Ippolito</name></author><author><name sortKey="Mchugh, T D" uniqKey="Mchugh T">T. D. McHugh</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Petersen, E" uniqKey="Petersen E">E. Petersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, X" uniqKey="Huang X">X. Huang</name></author><author><name sortKey="Li, M" uniqKey="Li M">M. Li</name></author><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y. Xu</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Meng, X" uniqKey="Meng X">X. Meng</name></author><author><name sortKey="An, X" uniqKey="An X">X. An</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Guo, L" uniqKey="Guo L">L. Guo</name></author><author><name sortKey="Shan, X" uniqKey="Shan X">X. Shan</name></author><author><name sortKey="Ge, J" uniqKey="Ge J">J. Ge</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Luo, Y" uniqKey="Luo Y">Y. Luo</name></author><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Jiang, Q" uniqKey="Jiang Q">Q. Jiang</name></author><author><name sortKey="Ning, X" uniqKey="Ning X">X. Ning</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, C K" uniqKey="Chang C">C. K. Chang</name></author><author><name sortKey="Lo, S C" uniqKey="Lo S">S. C. Lo</name></author><author><name sortKey="Wang, Y S" uniqKey="Wang Y">Y. S. Wang</name></author><author><name sortKey="Hou, M H" uniqKey="Hou M">M. H. Hou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Chan, J F" uniqKey="Chan J">J. F. Chan</name></author><author><name sortKey="Azhar, E I" uniqKey="Azhar E">E. I. Azhar</name></author><author><name sortKey="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K. Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcbride, R" uniqKey="Mcbride R">R. McBride</name></author><author><name sortKey="Van Zyl, M" uniqKey="Van Zyl M">M. van Zyl</name></author><author><name sortKey="Fielding, B C" uniqKey="Fielding B">B. C. Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De X0a Wit, E" uniqKey="De X0a Wit E">E. de
Wit</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N. van Doremalen</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="Munster, V J" uniqKey="Munster V">V. J. Munster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, S Y" uniqKey="Lin S">S. Y. Lin</name></author><author><name sortKey="Liu, C L" uniqKey="Liu C">C. L. Liu</name></author><author><name sortKey="Chang, Y M" uniqKey="Chang Y">Y. M. Chang</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Hou, M H" uniqKey="Hou M">M. H. Hou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nguyen, T X0a H V" uniqKey="Nguyen T">T.
H. V. Nguyen</name></author><author><name sortKey="Lichiere, J" uniqKey="Lichiere J">J. Lichiere</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B. Canard</name></author><author><name sortKey="Papageorgiou, N" uniqKey="Papageorgiou N">N. Papageorgiou</name></author><author><name sortKey="Attoumani, S" uniqKey="Attoumani S">S. Attoumani</name></author><author><name sortKey="Ferron, F" uniqKey="Ferron F">F. Ferron</name></author><author><name sortKey="Coutard, B" uniqKey="Coutard B">B. Coutard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, I J" uniqKey="Chen I">I. J. Chen</name></author><author><name sortKey="Yuann, J M" uniqKey="Yuann J">J. M. Yuann</name></author><author><name sortKey="Chang, Y M" uniqKey="Chang Y">Y. M. Chang</name></author><author><name sortKey="Lin, S Y" uniqKey="Lin S">S. Y. Lin</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Shen, Y Y" uniqKey="Shen Y">Y. Y. Shen</name></author><author><name sortKey="Huang, T H" uniqKey="Huang T">T. H. Huang</name></author><author><name sortKey="Hou, M H" uniqKey="Hou M">M. H. Hou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, H" uniqKey="Fan H">H. Fan</name></author><author><name sortKey="Ooi, A" uniqKey="Ooi A">A. Ooi</name></author><author><name sortKey="Tan, Y W" uniqKey="Tan Y">Y. W. Tan</name></author><author><name sortKey="Wang, S" uniqKey="Wang S">S. Wang</name></author><author><name sortKey="Fang, S" uniqKey="Fang S">S. Fang</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D. X. Liu</name></author><author><name sortKey="Lescar, J" uniqKey="Lescar J">J. Lescar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Sawyer, N" uniqKey="Sawyer N">N. Sawyer</name></author><author><name sortKey="Regan, L" uniqKey="Regan L">L. Regan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Papageorgiou, N" uniqKey="Papageorgiou N">N. Papageorgiou</name></author><author><name sortKey="Lichiere, J" uniqKey="Lichiere J">J. Lichiere</name></author><author><name sortKey="Baklouti, A" uniqKey="Baklouti A">A. Baklouti</name></author><author><name sortKey="Ferron, F" uniqKey="Ferron F">F. Ferron</name></author><author><name sortKey="Sevajol, M" uniqKey="Sevajol M">M. Sevajol</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B. Canard</name></author><author><name sortKey="Coutard, B" uniqKey="Coutard B">B. Coutard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jayaram, H" uniqKey="Jayaram H">H. Jayaram</name></author><author><name sortKey="Fan, H" uniqKey="Fan H">H. Fan</name></author><author><name sortKey="Bowman, B R" uniqKey="Bowman B">B. R. Bowman</name></author><author><name sortKey="Ooi, A" uniqKey="Ooi A">A. Ooi</name></author><author><name sortKey="Jayaram, J" uniqKey="Jayaram J">J. Jayaram</name></author><author><name sortKey="Collisson, E W" uniqKey="Collisson E">E. W. Collisson</name></author><author><name sortKey="Lescar, J" uniqKey="Lescar J">J. Lescar</name></author><author><name sortKey="Prasad, B V" uniqKey="Prasad B">B. V. Prasad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saikatendu, K S" uniqKey="Saikatendu K">K. S. Saikatendu</name></author><author><name sortKey="Joseph, J S" uniqKey="Joseph J">J. S. Joseph</name></author><author><name sortKey="Subramanian, V" uniqKey="Subramanian V">V. Subramanian</name></author><author><name sortKey="Neuman, B W" uniqKey="Neuman B">B. W. Neuman</name></author><author><name sortKey="Buchmeier, M J" uniqKey="Buchmeier M">M. J. Buchmeier</name></author><author><name sortKey="Stevens, R C" uniqKey="Stevens R">R. C. Stevens</name></author><author><name sortKey="Kuhn, P" uniqKey="Kuhn P">P. Kuhn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grossoehme, N E" uniqKey="Grossoehme N">N. E. Grossoehme</name></author><author><name sortKey="Li, L" uniqKey="Li L">L. Li</name></author><author><name sortKey="Keane, S C" uniqKey="Keane S">S. C. Keane</name></author><author><name sortKey="Liu, P" uniqKey="Liu P">P. Liu</name></author><author><name sortKey="Dann, C E" uniqKey="Dann C">C. E. Dann</name></author><author><name sortKey="Leibowitz, J L" uniqKey="Leibowitz J">J. L. Leibowitz</name></author><author><name sortKey="Giedroc, D P" uniqKey="Giedroc D">D. P. Giedroc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pyrkov, T V" uniqKey="Pyrkov T">T. V. Pyrkov</name></author><author><name sortKey="Chugunov, A O" uniqKey="Chugunov A">A. O. Chugunov</name></author><author><name sortKey="Krylov, N A" uniqKey="Krylov N">N. A. Krylov</name></author><author><name sortKey="Nolde, D E" uniqKey="Nolde D">D. E. Nolde</name></author><author><name sortKey="Efremov, R G" uniqKey="Efremov R">R. G. Efremov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Broos, J" uniqKey="Broos J">J. Broos</name></author><author><name sortKey="Tveen Jensen, K" uniqKey="Tveen Jensen K">K. Tveen-Jensen</name></author><author><name sortKey="De Waal, E" uniqKey="De Waal E">E. de Waal</name></author><author><name sortKey="Hesp, B H" uniqKey="Hesp B">B. H. Hesp</name></author><author><name sortKey="Jackson, J B" uniqKey="Jackson J">J. B. Jackson</name></author><author><name sortKey="Canters, G W" uniqKey="Canters G">G. W. Canters</name></author><author><name sortKey="Callis, P R" uniqKey="Callis P">P. R. Callis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gui, M" uniqKey="Gui M">M. Gui</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X. Liu</name></author><author><name sortKey="Guo, D" uniqKey="Guo D">D. Guo</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z. Zhang</name></author><author><name sortKey="Yin, C C" uniqKey="Yin C">C.-C. Yin</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="Xiang, Y" uniqKey="Xiang Y">Y. Xiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, C Y" uniqKey="Chen C">C. Y. Chen</name></author><author><name sortKey="Chang, C K" uniqKey="Chang C">C. K. Chang</name></author><author><name sortKey="Chang, Y W" uniqKey="Chang Y">Y. W. Chang</name></author><author><name sortKey="Sue, S C" uniqKey="Sue S">S. C. Sue</name></author><author><name sortKey="Bai, H I" uniqKey="Bai H">H. I. Bai</name></author><author><name sortKey="Riang, L" uniqKey="Riang L">L. Riang</name></author><author><name sortKey="Hsiao, C D" uniqKey="Hsiao C">C. D. Hsiao</name></author><author><name sortKey="Huang, T H" uniqKey="Huang T">T. H. Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wichapong, K" uniqKey="Wichapong K">K. Wichapong</name></author><author><name sortKey="Poelman, H" uniqKey="Poelman H">H. Poelman</name></author><author><name sortKey="Ercig, B" uniqKey="Ercig B">B. Ercig</name></author><author><name sortKey="Hrdinova, J" uniqKey="Hrdinova J">J. Hrdinova</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X. Liu</name></author><author><name sortKey="Lutgens, E" uniqKey="Lutgens E">E. Lutgens</name></author><author><name sortKey="Nicolaes, G A" uniqKey="Nicolaes G">G. A. Nicolaes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De X0a Vink, P J" uniqKey="De X0a Vink P">P. J. de
Vink</name></author><author><name sortKey="Andrei, S A" uniqKey="Andrei S">S. A. Andrei</name></author><author><name sortKey="Higuchi, Y" uniqKey="Higuchi Y">Y. Higuchi</name></author><author><name sortKey="Ottmann, C" uniqKey="Ottmann C">C. Ottmann</name></author><author><name sortKey="Milroy, L G" uniqKey="Milroy L">L. G. Milroy</name></author><author><name sortKey="Brunsveld, L" uniqKey="Brunsveld L">L. Brunsveld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blevitt, J M" uniqKey="Blevitt J">J. M. Blevitt</name></author><author><name sortKey="Hack, M D" uniqKey="Hack M">M. D. Hack</name></author><author><name sortKey="Herman, K L" uniqKey="Herman K">K. L. Herman</name></author><author><name sortKey="Jackson, P F" uniqKey="Jackson P">P. F. Jackson</name></author><author><name sortKey="Krawczuk, P J" uniqKey="Krawczuk P">P. J. Krawczuk</name></author><author><name sortKey="Lebsack, A D" uniqKey="Lebsack A">A. D. Lebsack</name></author><author><name sortKey="Liu, A X" uniqKey="Liu A">A. X. Liu</name></author><author><name sortKey="Mirzadegan, T" uniqKey="Mirzadegan T">T. Mirzadegan</name></author><author><name sortKey="Nelen, M I" uniqKey="Nelen M">M. I. Nelen</name></author><author><name sortKey="Patrick, A N" uniqKey="Patrick A">A. N. Patrick</name></author><author><name sortKey="Steinbacher, S" uniqKey="Steinbacher S">S. Steinbacher</name></author><author><name sortKey="Milla, M E" uniqKey="Milla M">M. E. Milla</name></author><author><name sortKey="Lumb, K J" uniqKey="Lumb K">K. J. Lumb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spencer Smith, R" uniqKey="Spencer Smith R">R. Spencer-Smith</name></author><author><name sortKey="Koide, A" uniqKey="Koide A">A. Koide</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y. Zhou</name></author><author><name sortKey="Eguchi, R R" uniqKey="Eguchi R">R. R. Eguchi</name></author><author><name sortKey="Sha, F" uniqKey="Sha F">F. Sha</name></author><author><name sortKey="Gajwani, P" uniqKey="Gajwani P">P. Gajwani</name></author><author><name sortKey="Santana, D" uniqKey="Santana D">D. Santana</name></author><author><name sortKey="Gupta, A" uniqKey="Gupta A">A. Gupta</name></author><author><name sortKey="Jacobs, M" uniqKey="Jacobs M">M. Jacobs</name></author><author><name sortKey="Herrero Garcia, E" uniqKey="Herrero Garcia E">E. Herrero-Garcia</name></author><author><name sortKey="Cobbert, J" uniqKey="Cobbert J">J. Cobbert</name></author><author><name sortKey="Lavoie, H" uniqKey="Lavoie H">H. Lavoie</name></author><author><name sortKey="Smith, M" uniqKey="Smith M">M. Smith</name></author><author><name sortKey="Rajakulendran, T" uniqKey="Rajakulendran T">T. Rajakulendran</name></author><author><name sortKey="Dowdell, E" uniqKey="Dowdell E">E. Dowdell</name></author><author><name sortKey="Okur, M N" uniqKey="Okur M">M. N. Okur</name></author><author><name sortKey="Dementieva, I" uniqKey="Dementieva I">I. Dementieva</name></author><author><name sortKey="Sicheri, F" uniqKey="Sicheri F">F. Sicheri</name></author><author><name sortKey="Therrien, M" uniqKey="Therrien M">M. Therrien</name></author><author><name sortKey="Hancock, J F" uniqKey="Hancock J">J. F. Hancock</name></author><author><name sortKey="Ikura, M" uniqKey="Ikura M">M. Ikura</name></author><author><name sortKey="Koide, S" uniqKey="Koide S">S. Koide</name></author><author><name sortKey="O Ryan, J P" uniqKey="O Ryan J">J. P. O’Bryan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pang, B" uniqKey="Pang B">B. Pang</name></author><author><name sortKey="Cheung, N N" uniqKey="Cheung N">N. N. Cheung</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Dai, J" uniqKey="Dai J">J. Dai</name></author><author><name sortKey="Kao, R Y" uniqKey="Kao R">R. Y. Kao</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name></author><author><name sortKey="Hao, Q" uniqKey="Hao Q">Q. Hao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kao, R Y" uniqKey="Kao R">R. Y. Kao</name></author><author><name sortKey="Yang, D" uniqKey="Yang D">D. Yang</name></author><author><name sortKey="Lau, L S" uniqKey="Lau L">L. S. Lau</name></author><author><name sortKey="Tsui, W H" uniqKey="Tsui W">W. H. Tsui</name></author><author><name sortKey="Hu, L" uniqKey="Hu L">L. Hu</name></author><author><name sortKey="Dai, J" uniqKey="Dai J">J. Dai</name></author><author><name sortKey="Chan, M P" uniqKey="Chan M">M. P. Chan</name></author><author><name sortKey="Chan, C M" uniqKey="Chan C">C. M. Chan</name></author><author><name sortKey="Wang, P" uniqKey="Wang P">P. Wang</name></author><author><name sortKey="Zheng, B J" uniqKey="Zheng B">B. J. Zheng</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J. Sun</name></author><author><name sortKey="Huang, J D" uniqKey="Huang J">J. D. Huang</name></author><author><name sortKey="Madar, J" uniqKey="Madar J">J. Madar</name></author><author><name sortKey="Chen, G" uniqKey="Chen G">G. Chen</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K. Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klenchin, V A" uniqKey="Klenchin V">V. A. Klenchin</name></author><author><name sortKey="King, R" uniqKey="King R">R. King</name></author><author><name sortKey="Tanaka, J" uniqKey="Tanaka J">J. Tanaka</name></author><author><name sortKey="Marriott, G" uniqKey="Marriott G">G. Marriott</name></author><author><name sortKey="Rayment, I" uniqKey="Rayment I">I. Rayment</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shin, I" uniqKey="Shin I">I. Shin</name></author><author><name sortKey="Hong, S" uniqKey="Hong S">S. Hong</name></author><author><name sortKey="Krische, M J" uniqKey="Krische M">M. J. Krische</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bubb, M R" uniqKey="Bubb M">M. R. Bubb</name></author><author><name sortKey="Spector, I" uniqKey="Spector I">I. Spector</name></author><author><name sortKey="Bershadsky, A D" uniqKey="Bershadsky A">A. D. Bershadsky</name></author><author><name sortKey="Korn, E D" uniqKey="Korn E">E. D. Korn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferreira X0a De Freitas, R" uniqKey="Ferreira X0a De Freitas R">R. Ferreira
de Freitas</name></author><author><name sortKey="Schapira, M" uniqKey="Schapira M">M. Schapira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hossain, B M" uniqKey="Hossain B">B. M. Hossain</name></author><author><name sortKey="Konermann, L" uniqKey="Konermann L">L. Konermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y S" uniqKey="Wang Y">Y. S. Wang</name></author><author><name sortKey="Chang, C K" uniqKey="Chang C">C. K. Chang</name></author><author><name sortKey="Hou, M H" uniqKey="Hou M">M. H. Hou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, P" uniqKey="Adams P">P. Adams</name></author><author><name sortKey="Grosse Kunstleve, R W" uniqKey="Grosse Kunstleve R">R. W. Grosse-Kunstleve</name></author><author><name sortKey="Hung, L W" uniqKey="Hung L">L.-W. Hung</name></author><author><name sortKey="Ioerger, T R" uniqKey="Ioerger T">T. R. Ioerger</name></author><author><name sortKey="Mccoy, A J" uniqKey="Mccoy A">A. J. McCoy</name></author><author><name sortKey="Moriarty, N" uniqKey="Moriarty N">N. Moriarty</name></author><author><name sortKey="Read, R J" uniqKey="Read R">R. J. Read</name></author><author><name sortKey="Sacchettini, J C" uniqKey="Sacchettini J">J. C. Sacchettini</name></author><author><name sortKey="Sauter, N" uniqKey="Sauter N">N. Sauter</name></author><author><name sortKey="Terwilliger, T" uniqKey="Terwilliger T">T. Terwilliger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P. Emsley</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K. Cowtan</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Petoukhov, M V" uniqKey="Petoukhov M">M. V. Petoukhov</name></author><author><name sortKey="Franke, D" uniqKey="Franke D">D. Franke</name></author><author><name sortKey="Shkumatov, A V" uniqKey="Shkumatov A">A. V. Shkumatov</name></author><author><name sortKey="Tria, G" uniqKey="Tria G">G. Tria</name></author><author><name sortKey="Kikhney, A G" uniqKey="Kikhney A">A. G. Kikhney</name></author><author><name sortKey="Gajda, M" uniqKey="Gajda M">M. Gajda</name></author><author><name sortKey="Gorba, C" uniqKey="Gorba C">C. Gorba</name></author><author><name sortKey="Mertens, H D" uniqKey="Mertens H">H. D. Mertens</name></author><author><name sortKey="Konarev, P V" uniqKey="Konarev P">P. V. Konarev</name></author><author><name sortKey="Svergun, D I" uniqKey="Svergun D">D. I. Svergun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Svergun, D" uniqKey="Svergun D">D. Svergun</name></author><author><name sortKey="Barberato, C" uniqKey="Barberato C">C. Barberato</name></author><author><name sortKey="Koch, M H J" uniqKey="Koch M">M. H. J. Koch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gunalan, V" uniqKey="Gunalan V">V. Gunalan</name></author><author><name sortKey="Mirazimi, A" uniqKey="Mirazimi A">A. Mirazimi</name></author><author><name sortKey="Tan, Y J" uniqKey="Tan Y">Y. J. Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Furuse, Y" uniqKey="Furuse Y">Y. Furuse</name></author><author><name sortKey="Okamoto, M" uniqKey="Okamoto M">M. Okamoto</name></author><author><name sortKey="Oshitani, H" uniqKey="Oshitani H">H. Oshitani</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">32105468</article-id><article-id pub-id-type="pmc">7094172</article-id><article-id pub-id-type="doi">10.1021/acs.jmedchem.9b01913</article-id><article-categories><subj-group><subject>Article</subject></subj-group></article-categories><title-group><article-title>Structure-Based
Stabilization of Non-native Protein–Protein
Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug
Design</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Lin</surname><given-names>Shan-Meng</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff2" ref-type="aff">‡</xref><xref rid="notes-3" ref-type="notes">○</xref></contrib><contrib contrib-type="author" id="ath2"><name><surname>Lin</surname><given-names>Shih-Chao</given-names></name><xref rid="aff3" ref-type="aff">§</xref><xref rid="notes-3" ref-type="notes">○</xref></contrib><contrib contrib-type="author" id="ath3"><name><surname>Hsu</surname><given-names>Jia-Ning</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff2" ref-type="aff">‡</xref><xref rid="notes-3" ref-type="notes">○</xref></contrib><contrib contrib-type="author" id="ath4"><name><surname>Chang</surname><given-names>Chung-ke</given-names></name><xref rid="aff5" ref-type="aff">⊥</xref><xref rid="notes-3" ref-type="notes">○</xref></contrib><contrib contrib-type="author" id="ath5"><name><surname>Chien</surname><given-names>Ching-Ming</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff2" ref-type="aff">‡</xref></contrib><contrib contrib-type="author" id="ath6"><name><surname>Wang</surname><given-names>Yong-Sheng</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath7"><name><surname>Wu</surname><given-names>Hung-Yi</given-names></name><xref rid="aff4" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" id="ath8"><name><surname>Jeng</surname><given-names>U-Ser</given-names></name><xref rid="aff6" ref-type="aff">#</xref><xref rid="aff7" ref-type="aff">∇</xref></contrib><contrib contrib-type="author" id="ath9"><name><surname>Kehn-Hall</surname><given-names>Kylene</given-names></name><xref rid="aff3" ref-type="aff">§</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath10"><name><surname>Hou</surname><given-names>Ming-Hon</given-names></name><xref rid="cor1" ref-type="other">*</xref><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff2" ref-type="aff">‡</xref></contrib><aff id="aff1"><label>†</label>Institute of Genomics and Bioinformatics,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></aff><aff id="aff2"><label>‡</label>Department of Life Sciences,<institution>National Chung Hsing University</institution>, Taichung 402,<country>Taiwan</country></aff><aff id="aff3"><label>§</label>National Center for Biodefense and Infectious Diseases, School of Systems Biology,<institution>George Mason University</institution>, Manassas, Virginia 20110,<country>United States</country></aff><aff id="aff4"><label>∥</label>Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine,<institution>National Chung Hsing University</institution>, Taichung 40227,<country>Taiwan</country></aff><aff id="aff5"><label>⊥</label><institution>Institute of Biomedical Sciences, Academia Sinica</institution>, Taipei 115,<country>Taiwan</country></aff><aff id="aff6"><label>#</label><institution>National Synchrotron Radiation Research Center</institution>, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu 30076,<country>Taiwan</country></aff><aff id="aff7"><label>∇</label>Department of Chemical Engineering,<institution>National Tsing Hua University</institution>, Hsinchu 30013,<country>Taiwan</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>Email: <email>mhho@nchu.edu.tw</email>. Tel.: <phone>+886-4-2284-0338</phone>. Fax: <fax>+886-4-2285-9329</fax> (ext. 7011).</corresp></author-notes><pub-date pub-type="epub"><day>27</day><month>02</month><year>2020</year></pub-date><pub-date pub-type="ppub"><day>26</day><month>03</month><year>2020</year></pub-date><volume>63</volume><issue>6</issue><fpage>3131</fpage><lpage>3141</lpage><history><date date-type="received"><day>19</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2020 American Chemical Society</copyright-statement><copyright-year>2020</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="jm9b01913_0005" id="ab-tgr1"></graphic></p><p>Structure-based
stabilization of protein–protein interactions
(PPIs) is a promising strategy for drug discovery. However, this approach
has mainly focused on the stabilization of native PPIs, and non-native
PPIs have received little consideration. Here, we identified a non-native
interaction interface on the three-dimensional dimeric structure of
the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV
N-NTD). The interface formed a conserved hydrophobic cavity suitable
for targeted drug screening. By considering the hydrophobic
complementarity during the virtual screening step, we identified 5-benzyloxygramine
as a new N protein PPI orthosteric stabilizer that exhibits both antiviral
and N-NTD protein-stabilizing activities. X-ray crystallography and
small-angle
X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD
dimers through simultaneous hydrophobic interactions with both partners,
resulting in abnormal N protein oligomerization that was further confirmed
in the cell. This unique approach based on the identification and
stabilization of non-native PPIs of N protein could be applied toward
drug discovery against CoV diseases.</p></abstract><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>jm9b01913</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>jm9b01913</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="d30e250"><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></record>Pour manipuler ce document sous Unix (Dilib)
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