Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure–activity relationship study
Identifieur interne : 000F91 ( Pmc/Curation ); précédent : 000F90; suivant : 000F92Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure–activity relationship study
Auteurs : Pillaiyar Thanigaimalai [Japon] ; Sho Konno [Japon] ; Takehito Yamamoto [Japon] ; Yuji Koiwai [Japon] ; Akihiro Taguchi [Japon] ; Kentaro Takayama [Japon] ; Fumika Yakushiji [Japon] ; Kenichi Akaji [Japon] ; Yoshiaki Kiso [Japon] ; Yuko Kawasaki [États-Unis] ; Shen-En Chen [États-Unis] ; Aurash Naser-Tavakolian [États-Unis] ; Arne Schön [États-Unis] ; Ernesto Freire [États-Unis] ; Yoshio Hayashi [Japon]Source :
- European Journal of Medicinal Chemistry [ 0223-5234 ] ; 2013.
Abstract
This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(pyrrolidone-3-yl)-2-benzothiazole (
Url:
DOI: 10.1016/j.ejmech.2013.05.005
PubMed: 23747811
PubMed Central: 7115367
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000F91
Links to Exploration step
PMC:7115367Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure–activity relationship study</title><author><name sortKey="Thanigaimalai, Pillaiyar" sort="Thanigaimalai, Pillaiyar" uniqKey="Thanigaimalai P" first="Pillaiyar" last="Thanigaimalai">Pillaiyar Thanigaimalai</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Konno, Sho" sort="Konno, Sho" uniqKey="Konno S" first="Sho" last="Konno">Sho Konno</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Yamamoto, Takehito" sort="Yamamoto, Takehito" uniqKey="Yamamoto T" first="Takehito" last="Yamamoto">Takehito Yamamoto</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Koiwai, Yuji" sort="Koiwai, Yuji" uniqKey="Koiwai Y" first="Yuji" last="Koiwai">Yuji Koiwai</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Taguchi, Akihiro" sort="Taguchi, Akihiro" uniqKey="Taguchi A" first="Akihiro" last="Taguchi">Akihiro Taguchi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Takayama, Kentaro" sort="Takayama, Kentaro" uniqKey="Takayama K" first="Kentaro" last="Takayama">Kentaro Takayama</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Yakushiji, Fumika" sort="Yakushiji, Fumika" uniqKey="Yakushiji F" first="Fumika" last="Yakushiji">Fumika Yakushiji</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Akaji, Kenichi" sort="Akaji, Kenichi" uniqKey="Akaji K" first="Kenichi" last="Akaji">Kenichi Akaji</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412</wicri:regionArea></affiliation></author><author><name sortKey="Kiso, Yoshiaki" sort="Kiso, Yoshiaki" uniqKey="Kiso Y" first="Yoshiaki" last="Kiso">Yoshiaki Kiso</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412</wicri:regionArea></affiliation></author><author><name sortKey="Kawasaki, Yuko" sort="Kawasaki, Yuko" uniqKey="Kawasaki Y" first="Yuko" last="Kawasaki">Yuko Kawasaki</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Shen En" sort="Chen, Shen En" uniqKey="Chen S" first="Shen-En" last="Chen">Shen-En Chen</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Naser Tavakolian, Aurash" sort="Naser Tavakolian, Aurash" uniqKey="Naser Tavakolian A" first="Aurash" last="Naser-Tavakolian">Aurash Naser-Tavakolian</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Schon, Arne" sort="Schon, Arne" uniqKey="Schon A" first="Arne" last="Schön">Arne Schön</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Freire, Ernesto" sort="Freire, Ernesto" uniqKey="Freire E" first="Ernesto" last="Freire">Ernesto Freire</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Hayashi, Yoshio" sort="Hayashi, Yoshio" uniqKey="Hayashi Y" first="Yoshio" last="Hayashi">Yoshio Hayashi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23747811</idno><idno type="pmc">7115367</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115367</idno><idno type="RBID">PMC:7115367</idno><idno type="doi">10.1016/j.ejmech.2013.05.005</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000F91</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F91</idno><idno type="wicri:Area/Pmc/Curation">000F91</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000F91</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure–activity relationship study</title><author><name sortKey="Thanigaimalai, Pillaiyar" sort="Thanigaimalai, Pillaiyar" uniqKey="Thanigaimalai P" first="Pillaiyar" last="Thanigaimalai">Pillaiyar Thanigaimalai</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Konno, Sho" sort="Konno, Sho" uniqKey="Konno S" first="Sho" last="Konno">Sho Konno</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Yamamoto, Takehito" sort="Yamamoto, Takehito" uniqKey="Yamamoto T" first="Takehito" last="Yamamoto">Takehito Yamamoto</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Koiwai, Yuji" sort="Koiwai, Yuji" uniqKey="Koiwai Y" first="Yuji" last="Koiwai">Yuji Koiwai</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Taguchi, Akihiro" sort="Taguchi, Akihiro" uniqKey="Taguchi A" first="Akihiro" last="Taguchi">Akihiro Taguchi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Takayama, Kentaro" sort="Takayama, Kentaro" uniqKey="Takayama K" first="Kentaro" last="Takayama">Kentaro Takayama</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Yakushiji, Fumika" sort="Yakushiji, Fumika" uniqKey="Yakushiji F" first="Fumika" last="Yakushiji">Fumika Yakushiji</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author><author><name sortKey="Akaji, Kenichi" sort="Akaji, Kenichi" uniqKey="Akaji K" first="Kenichi" last="Akaji">Kenichi Akaji</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412</wicri:regionArea></affiliation></author><author><name sortKey="Kiso, Yoshiaki" sort="Kiso, Yoshiaki" uniqKey="Kiso Y" first="Yoshiaki" last="Kiso">Yoshiaki Kiso</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412</wicri:regionArea></affiliation></author><author><name sortKey="Kawasaki, Yuko" sort="Kawasaki, Yuko" uniqKey="Kawasaki Y" first="Yuko" last="Kawasaki">Yuko Kawasaki</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Shen En" sort="Chen, Shen En" uniqKey="Chen S" first="Shen-En" last="Chen">Shen-En Chen</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Naser Tavakolian, Aurash" sort="Naser Tavakolian, Aurash" uniqKey="Naser Tavakolian A" first="Aurash" last="Naser-Tavakolian">Aurash Naser-Tavakolian</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Schon, Arne" sort="Schon, Arne" uniqKey="Schon A" first="Arne" last="Schön">Arne Schön</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Freire, Ernesto" sort="Freire, Ernesto" uniqKey="Freire E" first="Ernesto" last="Freire">Ernesto Freire</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, Johns Hopkins University, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Hayashi, Yoshio" sort="Hayashi, Yoshio" uniqKey="Hayashi Y" first="Yoshio" last="Hayashi">Yoshio Hayashi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea></affiliation></author></analytic><series><title level="j">European Journal of Medicinal Chemistry</title><idno type="ISSN">0223-5234</idno><idno type="eISSN">1768-3254</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(pyrrolidone-3-yl)-2-benzothiazole (<bold>8</bold>; <italic>K</italic><sub><italic>i</italic></sub> = 4.1 nM), in which the P3 valine unit was substituted with a variety of distinct moieties. The resulting series of dipeptide-type inhibitors displayed moderate to good inhibitory activities against 3CL<sup>pro</sup>. In particular, compounds <bold>26m</bold> and <bold>26n</bold> exhibited good inhibitory activities with <italic>K</italic><sub><italic>i</italic></sub> values of 0.39 and 0.33 μM, respectively. These low-molecular weight compounds are attractive leads for the further development of potent peptidomimetic inhibitors with pharmaceutical profiles. Docking studies were performed to model the binding interaction of the compound <bold>26m</bold> with the SARS-CoV 3CL protease. The preliminary SAR study of the peptidomimetic compounds with potent inhibitory activities revealed several structural features that boosted the inhibitory activity: (i) a benzothiazole warhead at the S1′ position, (ii) a γ-lactam unit at the S1-position, (iii) an appropriately hydrophobic leucine moiety at the S2-position, and (iv) a hydrogen bond between the <italic>N</italic>-arylglycine unit and a backbone hydrogen bond donor at the S3-position.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S. Gunther</name></author><author><name sortKey="Preiser, W" uniqKey="Preiser W">W. Preiser</name></author><author><name sortKey="Ven Der Werf, S" uniqKey="Ven Der Werf S">S. Ven der Werf</name></author><author><name sortKey="Brodt, H R" uniqKey="Brodt H">H.R. Brodt</name></author><author><name sortKey="Becker, S" uniqKey="Becker S">S. Becker</name></author><author><name sortKey="Rabenau, H" uniqKey="Rabenau H">H. Rabenau</name></author><author><name sortKey="Panning, M" uniqKey="Panning M">M. Panning</name></author><author><name sortKey="Kolensnikova, L" uniqKey="Kolensnikova L">L. Kolensnikova</name></author><author><name sortKey="Fouchier, R A M" uniqKey="Fouchier R">R.A.M. Fouchier</name></author><author><name sortKey="Berger, A" uniqKey="Berger A">A. Berger</name></author><author><name sortKey="Burguiere, A M" uniqKey="Burguiere A">A.M. Burguiere</name></author><author><name sortKey="Cinatl, J" uniqKey="Cinatl J">J. Cinatl</name></author><author><name sortKey="Eickmann, M" uniqKey="Eickmann M">M. Eickmann</name></author><author><name sortKey="Escriou, N" uniqKey="Escriou N">N. Escriou</name></author><author><name sortKey="Grywna, K" uniqKey="Grywna K">K. Grywna</name></author><author><name sortKey="Kramme, S" uniqKey="Kramme S">S. Kramme</name></author><author><name sortKey="Manuguerra, J" uniqKey="Manuguerra J">J. Manuguerra</name></author><author><name sortKey="Muller, S" uniqKey="Muller S">S. Muller</name></author><author><name sortKey="Rickerts, V" uniqKey="Rickerts V">V. Rickerts</name></author><author><name sortKey="Sturmer, M" uniqKey="Sturmer M">M. Sturmer</name></author><author><name sortKey="Vieth, S" uniqKey="Vieth S">S. Vieth</name></author><author><name sortKey="Klenk, H D" uniqKey="Klenk H">H.D. Klenk</name></author><author><name sortKey="Osterhaus, A D M E" uniqKey="Osterhaus A">A.D.M.E. Osterhaus</name></author><author><name sortKey="Schmitz, H" uniqKey="Schmitz H">H. Schmitz</name></author><author><name sortKey="Doerr, H W" uniqKey="Doerr H">H.W. Doerr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, N" uniqKey="Lee N">N. Lee</name></author><author><name sortKey="Hui, D" uniqKey="Hui D">D. Hui</name></author><author><name sortKey="Wu, A" uniqKey="Wu A">A. Wu</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author><author><name sortKey="Cameron, P" uniqKey="Cameron P">P. Cameron</name></author><author><name sortKey="Joynt, F M" uniqKey="Joynt F">F.M. Joynt</name></author><author><name sortKey="Ahuja, A" uniqKey="Ahuja A">A. Ahuja</name></author><author><name sortKey="Yung, M Y" uniqKey="Yung M">M.Y. Yung</name></author><author><name sortKey="Leung, C B" uniqKey="Leung C">C.B. Leung</name></author><author><name sortKey="To, K F" uniqKey="To K">K.F. To</name></author><author><name sortKey="Leu, M D" uniqKey="Leu M">M.D. Leu</name></author><author><name sortKey="Szeto, C C" uniqKey="Szeto C">C.C. Szeto</name></author><author><name sortKey="Chung, S" uniqKey="Chung S">S. Chung</name></author><author><name sortKey="Sung, J J Y" uniqKey="Sung J">J.J.Y. Sung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ksiazek, T G" uniqKey="Ksiazek T">T.G. Ksiazek</name></author><author><name sortKey="Erdman, D" uniqKey="Erdman D">D. Erdman</name></author><author><name sortKey="Goldsmith, C S" uniqKey="Goldsmith C">C.S. Goldsmith</name></author><author><name sortKey="Zaki, S R" uniqKey="Zaki S">S.R. Zaki</name></author><author><name sortKey="Peret, T" uniqKey="Peret T">T. Peret</name></author><author><name sortKey="Emery, S" uniqKey="Emery S">S. Emery</name></author><author><name sortKey="Tong, S" uniqKey="Tong S">S. Tong</name></author><author><name sortKey="Urbani, C" uniqKey="Urbani C">C. Urbani</name></author><author><name sortKey="Comer, J A" uniqKey="Comer J">J.A. Comer</name></author><author><name sortKey="Lim, W" uniqKey="Lim W">W. Lim</name></author><author><name sortKey="Rollin, P E" uniqKey="Rollin P">P.E. Rollin</name></author><author><name sortKey="Dowell, S F" uniqKey="Dowell S">S.F. Dowell</name></author><author><name sortKey="Ling, A E" uniqKey="Ling A">A.E. Ling</name></author><author><name sortKey="Humphrey, C D" uniqKey="Humphrey C">C.D. Humphrey</name></author><author><name sortKey="Shieh, W J" uniqKey="Shieh W">W.J. Shieh</name></author><author><name sortKey="Guarner, J" uniqKey="Guarner J">J. Guarner</name></author><author><name sortKey="Paddock, C D" uniqKey="Paddock C">C.D. Paddock</name></author><author><name sortKey="Rota, P" uniqKey="Rota P">P. Rota</name></author><author><name sortKey="Fields, B" uniqKey="Fields B">B. Fields</name></author><author><name sortKey="Derisi, J" uniqKey="Derisi J">J. DeRisi</name></author><author><name sortKey="Yang, J Y" uniqKey="Yang J">J.Y. Yang</name></author><author><name sortKey="Cox, N" uniqKey="Cox N">N. Cox</name></author><author><name sortKey="Hughes, J M" uniqKey="Hughes J">J.M. Hughes</name></author><author><name sortKey="Leduc, J W" uniqKey="Leduc J">J.W. LeDuc</name></author><author><name sortKey="Bellini, W J" uniqKey="Bellini W">W.J. Bellini</name></author><author><name sortKey="Anderson, L J" uniqKey="Anderson L">L.J. Anderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anand, K" uniqKey="Anand K">K. Anand</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Wadhwani, P" uniqKey="Wadhwani P">P. Wadhwani</name></author><author><name sortKey="Mesturs, J R" uniqKey="Mesturs J">J.R. Mesturs</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, J S" uniqKey="Peiris J">J.S. Peiris</name></author><author><name sortKey="Lai, S T" uniqKey="Lai S">S.T. Lai</name></author><author><name sortKey="Poon, L L" uniqKey="Poon L">L.L. Poon</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author><author><name sortKey="Yam, L Y" uniqKey="Yam L">L.Y. Yam</name></author><author><name sortKey="Lim, W" uniqKey="Lim W">W. Lim</name></author><author><name sortKey="Nicholls, J" uniqKey="Nicholls J">J. Nicholls</name></author><author><name sortKey="Yee, W K" uniqKey="Yee W">W.K. Yee</name></author><author><name sortKey="Yan, W W" uniqKey="Yan W">W.W. Yan</name></author><author><name sortKey="Cheung, M T" uniqKey="Cheung M">M.T. Cheung</name></author><author><name sortKey="Cheng, V C" uniqKey="Cheng V">V.C. Cheng</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.H. Chan</name></author><author><name sortKey="Tsang, D N" uniqKey="Tsang D">D.N. Tsang</name></author><author><name sortKey="Yung, R W" uniqKey="Yung R">R.W. Yung</name></author><author><name sortKey="Ng, T K" uniqKey="Ng T">T.K. Ng</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rota, P A" uniqKey="Rota P">P.A. Rota</name></author><author><name sortKey="Oberste, M S" uniqKey="Oberste M">M.S. Oberste</name></author><author><name sortKey="Monroe, S S" uniqKey="Monroe S">S.S. Monroe</name></author><author><name sortKey="Nix, W A" uniqKey="Nix W">W.A. Nix</name></author><author><name sortKey="Campagnoli, R" uniqKey="Campagnoli R">R. Campagnoli</name></author><author><name sortKey="Icenogle, J P" uniqKey="Icenogle J">J.P. Icenogle</name></author><author><name sortKey="Penaranda, S" uniqKey="Penaranda S">S. Penaranda</name></author><author><name sortKey="Bankamp, B" uniqKey="Bankamp B">B. Bankamp</name></author><author><name sortKey="Maher, K" uniqKey="Maher K">K. Maher</name></author><author><name sortKey="Chem, M H" uniqKey="Chem M">M.H. Chem</name></author><author><name sortKey="Tong, W" uniqKey="Tong W">W. Tong</name></author><author><name sortKey="Tamin, A" uniqKey="Tamin A">A. Tamin</name></author><author><name sortKey="Lowe, L" uniqKey="Lowe L">L. Lowe</name></author><author><name sortKey="Frace, M" uniqKey="Frace M">M. Frace</name></author><author><name sortKey="Derisi, J L" uniqKey="Derisi J">J.L. DeRisi</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q. Chen</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D. Wang</name></author><author><name sortKey="Erdman, D D" uniqKey="Erdman D">D.D. Erdman</name></author><author><name sortKey="Peret, T C" uniqKey="Peret T">T.C. Peret</name></author><author><name sortKey="Burns, C" uniqKey="Burns C">C. Burns</name></author><author><name sortKey="Ksiazek, T G" uniqKey="Ksiazek T">T.G. Ksiazek</name></author><author><name sortKey="Rollin, P E" uniqKey="Rollin P">P.E. Rollin</name></author><author><name sortKey="Sanchez, A" uniqKey="Sanchez A">A. Sanchez</name></author><author><name sortKey="Liffick, S" uniqKey="Liffick S">S. Liffick</name></author><author><name sortKey="Holloway, B" uniqKey="Holloway B">B. Holloway</name></author><author><name sortKey="Limor, J" uniqKey="Limor J">J. Limor</name></author><author><name sortKey="Mccaustland, K" uniqKey="Mccaustland K">K. McCaustland</name></author><author><name sortKey="Olsen Rasmussen, M" uniqKey="Olsen Rasmussen M">M. Olsen-Rasmussen</name></author><author><name sortKey="Fouchier, R" uniqKey="Fouchier R">R. Fouchier</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S. Gunther</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Pallansch, M A" uniqKey="Pallansch M">M.A. Pallansch</name></author><author><name sortKey="Anderson, L J" uniqKey="Anderson L">L.J. Anderson</name></author><author><name sortKey="Bellini, W J" uniqKey="Bellini W">W.J. Bellini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marra, M A" uniqKey="Marra M">M.A. Marra</name></author><author><name sortKey="Jones, S J" uniqKey="Jones S">S.J. Jones</name></author><author><name sortKey="Astell, C R" uniqKey="Astell C">C.R. Astell</name></author><author><name sortKey="Holt, R A" uniqKey="Holt R">R.A. Holt</name></author><author><name sortKey="Brooks Wilson, A" uniqKey="Brooks Wilson A">A. Brooks-Wilson</name></author><author><name sortKey="Butterfield, Y S" uniqKey="Butterfield Y">Y.S. Butterfield</name></author><author><name sortKey="Khattra, J" uniqKey="Khattra J">J. Khattra</name></author><author><name sortKey="Asano, J K" uniqKey="Asano J">J.K. Asano</name></author><author><name sortKey="Barber, S A" uniqKey="Barber S">S.A. Barber</name></author><author><name sortKey="Chan, S Y" uniqKey="Chan S">S.Y. Chan</name></author><author><name sortKey="Cloutier, A" uniqKey="Cloutier A">A. Cloutier</name></author><author><name sortKey="Coughlin, S M" uniqKey="Coughlin S">S.M. Coughlin</name></author><author><name sortKey="Freeman, D" uniqKey="Freeman D">D. Freeman</name></author><author><name sortKey="Girn, N" uniqKey="Girn N">N. Girn</name></author><author><name sortKey="Griffith, O L" uniqKey="Griffith O">O.L. Griffith</name></author><author><name sortKey="Leach, S R" uniqKey="Leach S">S.R. Leach</name></author><author><name sortKey="Mayo, M" uniqKey="Mayo M">M. Mayo</name></author><author><name sortKey="Mcdonald, H" uniqKey="Mcdonald H">H. McDonald</name></author><author><name sortKey="Montgomery, S B" uniqKey="Montgomery S">S.B. Montgomery</name></author><author><name sortKey="Pandoh, P K" uniqKey="Pandoh P">P.K. Pandoh</name></author><author><name sortKey="Petrescu, A S" uniqKey="Petrescu A">A.S. Petrescu</name></author><author><name sortKey="Robertson, A G" uniqKey="Robertson A">A.G. Robertson</name></author><author><name sortKey="Schein, J E" uniqKey="Schein J">J.E. Schein</name></author><author><name sortKey="Siddiqui, A" uniqKey="Siddiqui A">A. Siddiqui</name></author><author><name sortKey="Smailus, D E" uniqKey="Smailus D">D.E. Smailus</name></author><author><name sortKey="Sott, J M" uniqKey="Sott J">J.M. Sott</name></author><author><name sortKey="Yang, G S" uniqKey="Yang G">G.S. Yang</name></author><author><name sortKey="Plummer, F" uniqKey="Plummer F">F. Plummer</name></author><author><name sortKey="Andonov, A" uniqKey="Andonov A">A. Andonov</name></author><author><name sortKey="Artsob, H" uniqKey="Artsob H">H. Artsob</name></author><author><name sortKey="Bastien, N" uniqKey="Bastien N">N. Bastien</name></author><author><name sortKey="Bermard, K" uniqKey="Bermard K">K. Bermard</name></author><author><name sortKey="Booth, T F" uniqKey="Booth T">T.F. Booth</name></author><author><name sortKey="Bowness, D" uniqKey="Bowness D">D. Bowness</name></author><author><name sortKey="Czub, M" uniqKey="Czub M">M. Czub</name></author><author><name sortKey="Drebot, M" uniqKey="Drebot M">M. Drebot</name></author><author><name sortKey="Fernando, L" uniqKey="Fernando L">L. Fernando</name></author><author><name sortKey="Flick, R" uniqKey="Flick R">R. Flick</name></author><author><name sortKey="Garbutt, M" uniqKey="Garbutt M">M. Garbutt</name></author><author><name sortKey="Gray, M" uniqKey="Gray M">M. Gray</name></author><author><name sortKey="Grolla, A" uniqKey="Grolla A">A. Grolla</name></author><author><name sortKey="Jones, S" uniqKey="Jones S">S. Jones</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H. Feldmann</name></author><author><name sortKey="Meyers, A" uniqKey="Meyers A">A. Meyers</name></author><author><name sortKey="Kabani, A" uniqKey="Kabani A">A. Kabani</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Normand, S" uniqKey="Normand S">S. Normand</name></author><author><name sortKey="Stroher, U" uniqKey="Stroher U">U. Stroher</name></author><author><name sortKey="Tipples, G A" uniqKey="Tipples G">G.A. Tipples</name></author><author><name sortKey="Tyler, S" uniqKey="Tyler S">S. Tyler</name></author><author><name sortKey="Vogrig, R" uniqKey="Vogrig R">R. Vogrig</name></author><author><name sortKey="Ward, D" uniqKey="Ward D">D. Ward</name></author><author><name sortKey="Watson, B" uniqKey="Watson B">B. Watson</name></author><author><name sortKey="Brunham, R C" uniqKey="Brunham R">R.C. Brunham</name></author><author><name sortKey="Krajden, M" uniqKey="Krajden M">M. Krajden</name></author><author><name sortKey="Petric, M" uniqKey="Petric M">M. Petric</name></author><author><name sortKey="Skowronski, D M" uniqKey="Skowronski D">D.M. Skowronski</name></author><author><name sortKey="Upton, C" uniqKey="Upton C">C. Upton</name></author><author><name sortKey="Roper, R L" uniqKey="Roper R">R.L. Roper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thiel, V" uniqKey="Thiel V">V. Thiel</name></author><author><name sortKey="Ivanov, K A" uniqKey="Ivanov K">K.A. Ivanov</name></author><author><name sortKey="Putics, A A" uniqKey="Putics A">A.A. Putics</name></author><author><name sortKey="Hertzig, T" uniqKey="Hertzig T">T. Hertzig</name></author><author><name sortKey="Schelle, B" uniqKey="Schelle B">B. Schelle</name></author><author><name sortKey="Bayer, S" uniqKey="Bayer S">S. Bayer</name></author><author><name sortKey="Weiabrich, B" uniqKey="Weiabrich B">B. Weiabrich</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author><author><name sortKey="Rabenau, H" uniqKey="Rabenau H">H. Rabenau</name></author><author><name sortKey="Doerr, H W" uniqKey="Doerr H">H.W. Doerr</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Yang, M" uniqKey="Yang M">M. Yang</name></author><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y. Ding</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Lou, Z" uniqKey="Lou Z">Z. Lou</name></author><author><name sortKey="Zhou, Z" uniqKey="Zhou Z">Z. Zhou</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Mo, L" uniqKey="Mo L">L. Mo</name></author><author><name sortKey="Ye, S" uniqKey="Ye S">S. Ye</name></author><author><name sortKey="Pang, H" uniqKey="Pang H">H. Pang</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G.F. Gao</name></author><author><name sortKey="Anand, K" uniqKey="Anand K">K. Anand</name></author><author><name sortKey="Bartlam, M" uniqKey="Bartlam M">M. Bartlam</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author><author><name sortKey="Rao, Z" uniqKey="Rao Z">Z. Rao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chou, K" uniqKey="Chou K">K. Chou</name></author><author><name sortKey="Wei, D" uniqKey="Wei D">D. Wei</name></author><author><name sortKey="Zhong, W" uniqKey="Zhong W">W. Zhong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K. Pyrc</name></author><author><name sortKey="Berkhout, B" uniqKey="Berkhout B">B. Berkhout</name></author><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L. van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fielding, B C" uniqKey="Fielding B">B.C. Fielding</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 M E" uniqKey="Osterhaus A">A.D.M.E. Osterhaus</name></author><author><name sortKey="Fouchier, R A M" uniqKey="Fouchier R">R.A.M. Fouchier</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Shao, Y M" uniqKey="Shao Y">Y.M. Shao</name></author><author><name sortKey="Yang, W B" uniqKey="Yang W">W.B. Yang</name></author><author><name sortKey="Kuo, T H" uniqKey="Kuo T">T.H. Kuo</name></author><author><name sortKey="Tsai, K C" uniqKey="Tsai K">K.C. Tsai</name></author><author><name sortKey="Lin, C H" uniqKey="Lin C">C.H. Lin</name></author><author><name sortKey="Yang, A S" uniqKey="Yang A">A.S. Yang</name></author><author><name sortKey="Liang, P H" uniqKey="Liang P">P.H. Liang</name></author><author><name sortKey="Wong, C H" uniqKey="Wong C">C.H. Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jain, R P" uniqKey="Jain R">R.P. Jain</name></author><author><name sortKey="Pettersson, H I" uniqKey="Pettersson H">H.I. Pettersson</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Aull, K D" uniqKey="Aull K">K.D. Aull</name></author><author><name sortKey="Fortin, P D" uniqKey="Fortin P">P.D. Fortin</name></author><author><name sortKey="Huitema, C" uniqKey="Huitema C">C. Huitema</name></author><author><name sortKey="Eltis, L D" uniqKey="Eltis L">L.D. Eltis</name></author><author><name sortKey="Parrish, J C" uniqKey="Parrish J">J.C. Parrish</name></author><author><name sortKey="James, M N" uniqKey="James M">M.N. James</name></author><author><name sortKey="Wishart, D S" uniqKey="Wishart D">D.S. Wishart</name></author><author><name sortKey="Vederas, J C" uniqKey="Vederas J">J.C. Vederas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, S" uniqKey="Yang S">S. Yang</name></author><author><name sortKey="Chen, S J" uniqKey="Chen S">S.J. Chen</name></author><author><name sortKey="Hsu, M F" uniqKey="Hsu M">M.F. Hsu</name></author><author><name sortKey="Wu, J D" uniqKey="Wu J">J.D. Wu</name></author><author><name sortKey="Tseng, C T" uniqKey="Tseng C">C.T. Tseng</name></author><author><name sortKey="Liu, Y F" uniqKey="Liu Y">Y.F. Liu</name></author><author><name sortKey="Chen, H C" uniqKey="Chen H">H.C. Chen</name></author><author><name sortKey="Kuo, C W" uniqKey="Kuo C">C.W. Kuo</name></author><author><name sortKey="Wu, C S" uniqKey="Wu C">C.S. Wu</name></author><author><name sortKey="Chang, L W" uniqKey="Chang L">L.W. Chang</name></author><author><name sortKey="Chen, W C" uniqKey="Chen W">W.C. Chen</name></author><author><name sortKey="Liao, S Y" uniqKey="Liao S">S.Y. Liao</name></author><author><name sortKey="Chang, T Y" uniqKey="Chang T">T.Y. Chang</name></author><author><name sortKey="Hung, H H" uniqKey="Hung H">H.H. Hung</name></author><author><name sortKey="Shr, H L" uniqKey="Shr H">H.L. Shr</name></author><author><name sortKey="Liu, C Y" uniqKey="Liu C">C.Y. Liu</name></author><author><name sortKey="Huang, Y A" uniqKey="Huang Y">Y.A. Huang</name></author><author><name sortKey="Chang, L Y" uniqKey="Chang L">L.Y. Chang</name></author><author><name sortKey="Hsu, J C" uniqKey="Hsu J">J.C. Hsu</name></author><author><name sortKey="Peters, C J" uniqKey="Peters C">C.J. Peters</name></author><author><name sortKey="Wang, A H" uniqKey="Wang A">A.H. Wang</name></author><author><name sortKey="Hsu, M C" uniqKey="Hsu M">M.C. Hsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, T W" uniqKey="Lee T">T.W. Lee</name></author><author><name sortKey="Cherney, M M" uniqKey="Cherney M">M.M. Cherney</name></author><author><name sortKey="Huitema, C" uniqKey="Huitema C">C. Huitema</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="James, K E" uniqKey="James K">K.E. James</name></author><author><name sortKey="Powers, J C" uniqKey="Powers J">J.C. Powers</name></author><author><name sortKey="Eltis, L D" uniqKey="Eltis L">L.D. Eltis</name></author><author><name sortKey="James, M N G" uniqKey="James M">M.N.G. James</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akaji, K" uniqKey="Akaji K">K. Akaji</name></author><author><name sortKey="Konno, H" uniqKey="Konno H">H. Konno</name></author><author><name sortKey="Mitsui, H" uniqKey="Mitsui H">H. Mitsui</name></author><author><name sortKey="Teruya, K" uniqKey="Teruya K">K. Teruya</name></author><author><name sortKey="Shimamoto, Y" uniqKey="Shimamoto Y">Y. Shimamoto</name></author><author><name sortKey="Hattori, Y" uniqKey="Hattori Y">Y. Hattori</name></author><author><name sortKey="Ozaki, T" uniqKey="Ozaki T">T. Ozaki</name></author><author><name sortKey="Kusunoki, M" uniqKey="Kusunoki M">M. Kusunoki</name></author><author><name sortKey="Sanjoh, A" uniqKey="Sanjoh A">A. Sanjoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sydnes, M O" uniqKey="Sydnes M">M.O. Sydnes</name></author><author><name sortKey="Hayashi, Y" uniqKey="Hayashi Y">Y. Hayashi</name></author><author><name sortKey="Sharma, V K" uniqKey="Sharma V">V.K. Sharma</name></author><author><name sortKey="Hamada, T" uniqKey="Hamada T">T. Hamada</name></author><author><name sortKey="Bacha, U" uniqKey="Bacha U">U. Bacha</name></author><author><name sortKey="Barrila, J" uniqKey="Barrila J">J. Barrila</name></author><author><name sortKey="Freire, E" uniqKey="Freire E">E. Freire</name></author><author><name sortKey="Kiso, Y" uniqKey="Kiso Y">Y. Kiso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Regnier, T" uniqKey="Regnier T">T. Regnier</name></author><author><name sortKey="Sharma, D" uniqKey="Sharma D">D. Sharma</name></author><author><name sortKey="Hidaka, K" uniqKey="Hidaka K">K. Hidaka</name></author><author><name sortKey="Bacha, U" uniqKey="Bacha U">U. Bacha</name></author><author><name sortKey="Freire, E" uniqKey="Freire E">E. Freire</name></author><author><name sortKey="Hayashi, Y" uniqKey="Hayashi Y">Y. Hayashi</name></author><author><name sortKey="Kiso, Y" uniqKey="Kiso Y">Y. Kiso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Konno, S" uniqKey="Konno S">S. Konno</name></author><author><name sortKey="Thanigaimalai, P" uniqKey="Thanigaimalai P">P. Thanigaimalai</name></author><author><name sortKey="Nakada, K" uniqKey="Nakada K">K. Nakada</name></author><author><name sortKey="Yamamoto, T" uniqKey="Yamamoto T">T. Yamamoto</name></author><author><name sortKey="Yamazaki, Y" uniqKey="Yamazaki Y">Y. Yamazaki</name></author><author><name sortKey="Yakushiji, F" uniqKey="Yakushiji F">F. Yakushiji</name></author><author><name sortKey="Akaji, K" uniqKey="Akaji K">K. Akaji</name></author><author><name sortKey="Kiso, Y" uniqKey="Kiso Y">Y. Kiso</name></author><author><name sortKey="Kawasaki, Y" uniqKey="Kawasaki Y">Y. Kawasaki</name></author><author><name sortKey="Freire, E" uniqKey="Freire E">E. Freire</name></author><author><name sortKey="Hayashi, Y" uniqKey="Hayashi Y">Y. Hayashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaeppler, U" uniqKey="Kaeppler U">U. Kaeppler</name></author><author><name sortKey="Stiefl, N" uniqKey="Stiefl N">N. Stiefl</name></author><author><name sortKey="Schiller, M" uniqKey="Schiller M">M. Schiller</name></author><author><name sortKey="Vicik, R" uniqKey="Vicik R">R. Vicik</name></author><author><name sortKey="Breuning, A" uniqKey="Breuning A">A. Breuning</name></author><author><name sortKey="Schmitz, W" uniqKey="Schmitz W">W. Schmitz</name></author><author><name sortKey="Rupprecht, D" uniqKey="Rupprecht D">D. Rupprecht</name></author><author><name sortKey="Schmuck, C" uniqKey="Schmuck C">C. Schmuck</name></author><author><name sortKey="Baumann, K" uniqKey="Baumann K">K. Baumann</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Schirmeister, T" uniqKey="Schirmeister T">T. Schirmeister</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L. Chen</name></author><author><name sortKey="Gui, C" uniqKey="Gui C">C. Gui</name></author><author><name sortKey="Luo, X" uniqKey="Luo X">X. Luo</name></author><author><name sortKey="Yang, Q" uniqKey="Yang Q">Q. Yang</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S. Gunther</name></author><author><name sortKey="Scandella, E" uniqKey="Scandella E">E. Scandella</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Bai, D" uniqKey="Bai D">D. Bai</name></author><author><name sortKey="He, X" uniqKey="He X">X. He</name></author><author><name sortKey="Ludewig, B" uniqKey="Ludewig B">B. Ludewig</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Luo, H" uniqKey="Luo H">H. Luo</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Zou, J" uniqKey="Zou J">J. Zou</name></author><author><name sortKey="Thiel, V" uniqKey="Thiel V">V. Thiel</name></author><author><name sortKey="Chen, K" uniqKey="Chen K">K. Chen</name></author><author><name sortKey="Shen, J" uniqKey="Shen J">J. Shen</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X. Shen</name></author><author><name sortKey="Jiang, H" uniqKey="Jiang H">H. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blanchard, J E" uniqKey="Blanchard J">J.E. Blanchard</name></author><author><name sortKey="Elowe, N H" uniqKey="Elowe N">N.H. Elowe</name></author><author><name sortKey="Huitema, C" uniqKey="Huitema C">C. Huitema</name></author><author><name sortKey="Fortin, P D" uniqKey="Fortin P">P.D. Fortin</name></author><author><name sortKey="Cechetto, J D" uniqKey="Cechetto J">J.D. Cechetto</name></author><author><name sortKey="Eltis, L D" uniqKey="Eltis L">L.D. Eltis</name></author><author><name sortKey="Brown, E D" uniqKey="Brown E">E.D. Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, L" uniqKey="Zhou L">L. Zhou</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Wei, P" uniqKey="Wei P">P. Wei</name></author><author><name sortKey="Huang, C" uniqKey="Huang C">C. Huang</name></author><author><name sortKey="Pei, J" uniqKey="Pei J">J. Pei</name></author><author><name sortKey="Yuan, Y" uniqKey="Yuan Y">Y. Yuan</name></author><author><name sortKey="Lai, L" uniqKey="Lai L">L. Lai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, C Y" uniqKey="Wu C">C.Y. Wu</name></author><author><name sortKey="King, K Y" uniqKey="King K">K.Y. King</name></author><author><name sortKey="Kuo, C J" uniqKey="Kuo C">C.J. Kuo</name></author><author><name sortKey="Fang, J M" uniqKey="Fang J">J.M. Fang</name></author><author><name sortKey="Wu, Y T" uniqKey="Wu Y">Y.T. Wu</name></author><author><name sortKey="Ho, M Y" uniqKey="Ho M">M.Y. Ho</name></author><author><name sortKey="Liao, C L" uniqKey="Liao C">C.L. Liao</name></author><author><name sortKey="Shie, J J" uniqKey="Shie J">J.J. Shie</name></author><author><name sortKey="Liang, P H" uniqKey="Liang P">P.H. Liang</name></author><author><name sortKey="Wong, C H" uniqKey="Wong C">C.H. Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ramajayam, R" uniqKey="Ramajayam R">R. Ramajayam</name></author><author><name sortKey="Tan, K P" uniqKey="Tan K">K.P. Tan</name></author><author><name sortKey="Liu, H G" uniqKey="Liu H">H.G. Liu</name></author><author><name sortKey="Liang, P H" uniqKey="Liang P">P.H. Liang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ramajayam, R" uniqKey="Ramajayam R">R. Ramajayam</name></author><author><name sortKey="Tan, K P" uniqKey="Tan K">K.P. Tan</name></author><author><name sortKey="Liu, H G" uniqKey="Liu H">H.G. Liu</name></author><author><name sortKey="Liang, P H" uniqKey="Liang P">P.H. Liang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mukherjee, P" uniqKey="Mukherjee P">P. Mukherjee</name></author><author><name sortKey="Desai, P" uniqKey="Desai P">P. Desai</name></author><author><name sortKey="Ross, L" uniqKey="Ross L">L. Ross</name></author><author><name sortKey="White, E L" uniqKey="White E">E.L. White</name></author><author><name sortKey="Avery, M A" uniqKey="Avery M">M.A. Avery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tian, Q" uniqKey="Tian Q">Q. Tian</name></author><author><name sortKey="Nayyar, N K" uniqKey="Nayyar N">N.K. Nayyar</name></author><author><name sortKey="Babu, S" uniqKey="Babu S">S. Babu</name></author><author><name sortKey="Chen, L" uniqKey="Chen L">L. Chen</name></author><author><name sortKey="Tao, J" uniqKey="Tao J">J. Tao</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Tibbetts, A" uniqKey="Tibbetts A">A. Tibbetts</name></author><author><name sortKey="Moran, T" uniqKey="Moran T">T. Moran</name></author><author><name sortKey="Liou, J" uniqKey="Liou J">J. Liou</name></author><author><name sortKey="Guo, M" uniqKey="Guo M">M. Guo</name></author><author><name sortKey="Kennedy, T P" uniqKey="Kennedy T">T.P. Kennedy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bacha, U" uniqKey="Bacha U">U. Bacha</name></author><author><name sortKey="Barrila, J" uniqKey="Barrila J">J. Barrila</name></author><author><name sortKey="Gabelli, B" uniqKey="Gabelli B">B. Gabelli</name></author><author><name sortKey="Kiso, Y" uniqKey="Kiso Y">Y. Kiso</name></author><author><name sortKey="Amzel, L M" uniqKey="Amzel L">L.M. Amzel</name></author><author><name sortKey="Freire, E" uniqKey="Freire E">E. Freire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barrila, J" uniqKey="Barrila J">J. Barrila</name></author><author><name sortKey="Bacha, U" uniqKey="Bacha U">U. Bacha</name></author><author><name sortKey="Freire, E" uniqKey="Freire E">E. Freire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akaji, K" uniqKey="Akaji K">K. Akaji</name></author><author><name sortKey="Konno, H" uniqKey="Konno H">H. Konno</name></author><author><name sortKey="Onozuka, M" uniqKey="Onozuka M">M. Onozuka</name></author><author><name sortKey="Makino, A" uniqKey="Makino A">A. Makino</name></author><author><name sortKey="Saito, H" uniqKey="Saito H">H. Saito</name></author><author><name sortKey="Nosaka, K" uniqKey="Nosaka K">K. Nosaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Xie, W" uniqKey="Xie W">W. Xie</name></author><author><name sortKey="Xue, X" uniqKey="Xue X">X. Xue</name></author><author><name sortKey="Yang, K" uniqKey="Yang K">K. Yang</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J. Ma</name></author><author><name sortKey="Liang, W" uniqKey="Liang W">W. Liang</name></author><author><name sortKey="Zhao, Q" uniqKey="Zhao Q">Q. Zhao</name></author><author><name sortKey="Zhou, Z" uniqKey="Zhou Z">Z. Zhou</name></author><author><name sortKey="Pei, D" uniqKey="Pei D">D. Pei</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author><author><name sortKey="Wong, L" uniqKey="Wong L">L. Wong</name></author><author><name sortKey="Gao, G" uniqKey="Gao G">G. Gao</name></author><author><name sortKey="Chen, S" uniqKey="Chen S">S. Chen</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author><author><name sortKey="Ma, D" uniqKey="Ma D">D. Ma</name></author><author><name sortKey="Bartlam, M" uniqKey="Bartlam M">M. Bartlam</name></author><author><name sortKey="Rao, Z" uniqKey="Rao Z">Z. Rao</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Eur J Med Chem</journal-id><journal-id journal-id-type="iso-abbrev">Eur J Med Chem</journal-id><journal-title-group><journal-title>European Journal of Medicinal Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0223-5234</issn><issn pub-type="epub">1768-3254</issn><publisher><publisher-name>Elsevier Masson SAS.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23747811</article-id><article-id pub-id-type="pmc">7115367</article-id><article-id pub-id-type="publisher-id">S0223-5234(13)00305-X</article-id><article-id pub-id-type="doi">10.1016/j.ejmech.2013.05.005</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure–activity relationship study</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Thanigaimalai</surname><given-names>Pillaiyar</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Konno</surname><given-names>Sho</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Yamamoto</surname><given-names>Takehito</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Koiwai</surname><given-names>Yuji</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Taguchi</surname><given-names>Akihiro</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Takayama</surname><given-names>Kentaro</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Yakushiji</surname><given-names>Fumika</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au8"><name><surname>Akaji</surname><given-names>Kenichi</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au9"><name><surname>Kiso</surname><given-names>Yoshiaki</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au10"><name><surname>Kawasaki</surname><given-names>Yuko</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au11"><name><surname>Chen</surname><given-names>Shen-En</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au12"><name><surname>Naser-Tavakolian</surname><given-names>Aurash</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au13"><name><surname>Schön</surname><given-names>Arne</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au14"><name><surname>Freire</surname><given-names>Ernesto</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au15"><name><surname>Hayashi</surname><given-names>Yoshio</given-names></name><email>yhayashi@toyaku.ac.jp</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan</aff><aff id="aff2"><label>b</label>Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan</aff><aff id="aff3"><label>c</label>Department of Biology, Johns Hopkins University, Baltimore, MD, USA</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Tel./fax: +81 42 676 3275. <email>yhayashi@toyaku.ac.jp</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>20</day><month>5</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>7</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>20</day><month>5</month><year>2013</year></pub-date><volume>65</volume><fpage>436</fpage><lpage>447</lpage><history><date date-type="received"><day>11</day><month>3</month><year>2013</year></date><date date-type="rev-recd"><day>20</day><month>4</month><year>2013</year></date><date date-type="accepted"><day>7</day><month>5</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Elsevier Masson SAS. All rights reserved.</copyright-statement><copyright-year>2013</copyright-year><copyright-holder>Elsevier Masson SAS</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights 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 free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="abs0010"><p>This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(pyrrolidone-3-yl)-2-benzothiazole (<bold>8</bold>; <italic>K</italic><sub><italic>i</italic></sub> = 4.1 nM), in which the P3 valine unit was substituted with a variety of distinct moieties. The resulting series of dipeptide-type inhibitors displayed moderate to good inhibitory activities against 3CL<sup>pro</sup>. In particular, compounds <bold>26m</bold> and <bold>26n</bold> exhibited good inhibitory activities with <italic>K</italic><sub><italic>i</italic></sub> values of 0.39 and 0.33 μM, respectively. These low-molecular weight compounds are attractive leads for the further development of potent peptidomimetic inhibitors with pharmaceutical profiles. Docking studies were performed to model the binding interaction of the compound <bold>26m</bold> with the SARS-CoV 3CL protease. The preliminary SAR study of the peptidomimetic compounds with potent inhibitory activities revealed several structural features that boosted the inhibitory activity: (i) a benzothiazole warhead at the S1′ position, (ii) a γ-lactam unit at the S1-position, (iii) an appropriately hydrophobic leucine moiety at the S2-position, and (iv) a hydrogen bond between the <italic>N</italic>-arylglycine unit and a backbone hydrogen bond donor at the S3-position.</p></abstract><abstract abstract-type="graphical" id="abs0015"><title>Graphical abstract</title><fig id="undfig1" position="anchor"><graphic xlink:href="fx1"></graphic></fig></abstract><abstract abstract-type="author-highlights" id="abs0020"><title>Highlights</title><p><list list-type="simple" id="ulist0010"><list-item id="u0010"><label>•</label><p id="p0010">A series of dipeptide-type SARS CoV 3CL<sup>pro</sup> inhibitors were synthesized.</p></list-item><list-item id="u0015"><label>•</label><p id="p0015">Compounds have shown significant inhibitory activity.</p></list-item><list-item id="u0020"><label>•</label><p id="p0020">A potent compound was discovered by changing the P3 position.</p></list-item><list-item id="u0025"><label>•</label><p id="p0025">Compounds <bold>26m</bold> and <bold>26n</bold> displayed potent inhibitory activities.</p></list-item></list></p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>SARS</kwd><kwd>SARS-CoV 3CL protease</kwd><kwd>Peptidomimetics</kwd><kwd>Dipeptide</kwd><kwd>Cysteine protease inhibitors</kwd><kwd>Docking study</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F91 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000F91 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:7115367
|texte= Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure–activity relationship study
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:23747811" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |