X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases.
Identifieur interne : 001041 ( PubMed/Corpus ); précédent : 001040; suivant : 001042X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases.
Auteurs : Yahira M. Báez-Santos ; Scott J. Barraza ; Michael W. Wilson ; Michael P. Agius ; Anna M. Mielech ; Nicole M. Davis ; Susan C. Baker ; Scott D. Larsen ; Andrew D. MesecarSource :
- Journal of medicinal chemistry [ 1520-4804 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemical synthesis), Antiviral Agents (metabolism), Antiviral Agents (pharmacology), Cell Survival (drug effects), Chlorocebus aethiops, Coronavirus (drug effects), Coronavirus (enzymology), Cysteine Proteinase Inhibitors (chemical synthesis), Cysteine Proteinase Inhibitors (pharmacology), Humans, Indicators and Reagents, Molecular Conformation, Mutagenesis (drug effects), Papain (chemistry), Peptide Hydrolases (chemistry), Peptide Hydrolases (metabolism), Phospholipase A2 Inhibitors (chemical synthesis), Phospholipase A2 Inhibitors (pharmacology), Protein Binding, SARS Virus (drug effects), SARS Virus (enzymology), Structure-Activity Relationship, Vero Cells, X-Ray Diffraction.
- MESH :
- chemical , chemical synthesis : Antiviral Agents, Cysteine Proteinase Inhibitors, Phospholipase A2 Inhibitors.
- chemical , chemistry : Papain, Peptide Hydrolases.
- chemical , metabolism : Antiviral Agents, Peptide Hydrolases.
- chemical , pharmacology : Antiviral Agents, Cysteine Proteinase Inhibitors, Phospholipase A2 Inhibitors.
- drug effects : Cell Survival, Coronavirus, Mutagenesis, SARS Virus.
- enzymology : Coronavirus, SARS Virus.
- Animals, Chlorocebus aethiops, Humans, Indicators and Reagents, Molecular Conformation, Protein Binding, Structure-Activity Relationship, Vero Cells, X-Ray Diffraction.
Abstract
Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.
DOI: 10.1021/jm401712t
PubMed: 24568342
Links to Exploration step
pubmed:24568342Le document en format XML
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State Street, West Lafayette, Indiana 47907, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Barraza, Scott J" sort="Barraza, Scott J" uniqKey="Barraza S" first="Scott J" last="Barraza">Scott J. Barraza</name></author><author><name sortKey="Wilson, Michael W" sort="Wilson, Michael W" uniqKey="Wilson M" first="Michael W" last="Wilson">Michael W. Wilson</name></author><author><name sortKey="Agius, Michael P" sort="Agius, Michael P" uniqKey="Agius M" first="Michael P" last="Agius">Michael P. Agius</name></author><author><name sortKey="Mielech, Anna M" sort="Mielech, Anna M" uniqKey="Mielech A" first="Anna M" last="Mielech">Anna M. Mielech</name></author><author><name sortKey="Davis, Nicole M" sort="Davis, Nicole M" uniqKey="Davis N" first="Nicole M" last="Davis">Nicole M. Davis</name></author><author><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C" last="Baker">Susan C. Baker</name></author><author><name sortKey="Larsen, Scott D" sort="Larsen, Scott D" uniqKey="Larsen S" first="Scott D" last="Larsen">Scott D. Larsen</name></author><author><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D" last="Mesecar">Andrew D. Mesecar</name></author></analytic><series><title level="j">Journal of medicinal chemistry</title><idno type="eISSN">1520-4804</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (chemical synthesis)</term><term>Antiviral Agents (metabolism)</term><term>Antiviral Agents (pharmacology)</term><term>Cell Survival (drug effects)</term><term>Chlorocebus aethiops</term><term>Coronavirus (drug effects)</term><term>Coronavirus (enzymology)</term><term>Cysteine Proteinase Inhibitors (chemical synthesis)</term><term>Cysteine Proteinase Inhibitors (pharmacology)</term><term>Humans</term><term>Indicators and Reagents</term><term>Molecular Conformation</term><term>Mutagenesis (drug effects)</term><term>Papain (chemistry)</term><term>Peptide Hydrolases (chemistry)</term><term>Peptide Hydrolases (metabolism)</term><term>Phospholipase A2 Inhibitors (chemical synthesis)</term><term>Phospholipase A2 Inhibitors (pharmacology)</term><term>Protein Binding</term><term>SARS Virus (drug effects)</term><term>SARS Virus (enzymology)</term><term>Structure-Activity Relationship</term><term>Vero Cells</term><term>X-Ray Diffraction</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antiviral Agents</term><term>Cysteine Proteinase Inhibitors</term><term>Phospholipase A2 Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Papain</term><term>Peptide Hydrolases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiviral Agents</term><term>Peptide Hydrolases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Cysteine Proteinase Inhibitors</term><term>Phospholipase A2 Inhibitors</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term><term>Coronavirus</term><term>Mutagenesis</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Coronavirus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Indicators and Reagents</term><term>Molecular Conformation</term><term>Protein Binding</term><term>Structure-Activity Relationship</term><term>Vero Cells</term><term>X-Ray Diffraction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24568342</PMID><DateCompleted><Year>2014</Year><Month>05</Month><Day>27</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4804</ISSN><JournalIssue CitedMedium="Internet"><Volume>57</Volume><Issue>6</Issue><PubDate><Year>2014</Year><Month>Mar</Month><Day>27</Day></PubDate></JournalIssue><Title>Journal of medicinal chemistry</Title><ISOAbbreviation>J. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases.</ArticleTitle><Pagination><MedlinePgn>2393-412</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/jm401712t</ELocationID><Abstract><AbstractText>Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Báez-Santos</LastName><ForeName>Yahira M</ForeName><Initials>YM</Initials><AffiliationInfo><Affiliation>Department of Biological Sciences, Purdue University , 915 W. 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1;466(1):8-14</Citation><ArticleIdList><ArticleId IdType="pubmed">17692280</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2005 Dec;79(24):15189-98</Citation><ArticleIdList><ArticleId IdType="pubmed">16306590</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Med. 2005 Aug;2(8):e240</Citation><ArticleIdList><ArticleId IdType="pubmed">16104827</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2013;4(1):e00611-12</Citation><ArticleIdList><ArticleId IdType="pubmed">23422412</ArticleId></ArticleIdList></Reference><Reference><Citation>Infect Disord Drug Targets. 2009 Apr;9(2):223-45</Citation><ArticleIdList><ArticleId IdType="pubmed">19275708</ArticleId></ArticleIdList></Reference><Reference><Citation>Euro Surveill. 2012;17(40):20290</Citation><ArticleIdList><ArticleId IdType="pubmed">23078800</ArticleId></ArticleIdList></Reference><Reference><Citation>CRC Crit Rev Biochem. 1984;15(3):201-35</Citation><ArticleIdList><ArticleId IdType="pubmed">6370595</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2007 Nov 2;282(44):32208-21</Citation><ArticleIdList><ArticleId IdType="pubmed">17761676</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2012;3(6). pii: e00473-12. doi: 10.1128/mBio.00473-12</Citation><ArticleIdList><ArticleId IdType="pubmed">23170002</ArticleId></ArticleIdList></Reference><Reference><Citation>J Pharm Sci. 2000 Aug;89(8):1000-7</Citation><ArticleIdList><ArticleId IdType="pubmed">10906723</ArticleId></ArticleIdList></Reference><Reference><Citation>Nucleic Acids Res. 2004;32(14):e115</Citation><ArticleIdList><ArticleId IdType="pubmed">15304544</ArticleId></ArticleIdList></Reference><Reference><Citation>J Org Chem. 1946 Jul;11(4):390-4</Citation><ArticleIdList><ArticleId IdType="pubmed">20279696</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2005 Dec;79(24):15199-208</Citation><ArticleIdList><ArticleId IdType="pubmed">16306591</ArticleId></ArticleIdList></Reference><Reference><Citation>Euro Surveill. 2012;17(40):20292</Citation><ArticleIdList><ArticleId IdType="pubmed">23078799</ArticleId></ArticleIdList></Reference><Reference><Citation>Euro Surveill. 2012;17(39). pii: 20282</Citation><ArticleIdList><ArticleId IdType="pubmed">23041021</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2004 Dec;78(24):13600-12</Citation><ArticleIdList><ArticleId IdType="pubmed">15564471</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2012;7(2):e30802</Citation><ArticleIdList><ArticleId IdType="pubmed">22312431</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2013;4(1). pii: e00002-13. doi: 10.1128/mBio.00002-13</Citation><ArticleIdList><ArticleId IdType="pubmed">23322635</ArticleId></ArticleIdList></Reference><Reference><Citation>J Med Chem. 2009 Aug 27;52(16):5228-40</Citation><ArticleIdList><ArticleId IdType="pubmed">19645480</ArticleId></ArticleIdList></Reference><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21</Citation><ArticleIdList><ArticleId IdType="pubmed">20124702</ArticleId></ArticleIdList></Reference><Reference><Citation>J Med Chem. 2010 Jul 8;53(13):4968-79</Citation><ArticleIdList><ArticleId IdType="pubmed">20527968</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2013 Jul;87(14):7790-2</Citation><ArticleIdList><ArticleId IdType="pubmed">23678167</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16119-24</Citation><ArticleIdList><ArticleId IdType="pubmed">18852458</ArticleId></ArticleIdList></Reference><Reference><Citation>MMWR Morb Mortal Wkly Rep. 2013 Mar 15;62(10):194-5</Citation><ArticleIdList><ArticleId IdType="pubmed">23486385</ArticleId></ArticleIdList></Reference><Reference><Citation>ChemMedChem. 2013 Aug;8(8):1361-72</Citation><ArticleIdList><ArticleId IdType="pubmed">23788528</ArticleId></ArticleIdList></Reference><Reference><Citation>Drug Metab Rev. 1974;3(2):231-301</Citation><ArticleIdList><ArticleId IdType="pubmed">4423562</ArticleId></ArticleIdList></Reference><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3</Citation><ArticleIdList><ArticleId IdType="pubmed">15299374</ArticleId></ArticleIdList></Reference><Reference><Citation>Biophys Chem. 2003 Sep;105(2-3):221-30</Citation><ArticleIdList><ArticleId IdType="pubmed">14499894</ArticleId></ArticleIdList></Reference><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32</Citation><ArticleIdList><ArticleId IdType="pubmed">15572765</ArticleId></ArticleIdList></Reference><Reference><Citation>Bioorg Med Chem. 2013 Apr 1;21(7):1880-97</Citation><ArticleIdList><ArticleId IdType="pubmed">23433668</ArticleId></ArticleIdList></Reference><Reference><Citation>Methods Enzymol. 2003;374:300-21</Citation><ArticleIdList><ArticleId IdType="pubmed">14696379</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Pharmacol. 1984 Feb 15;33(4):577-80</Citation><ArticleIdList><ArticleId IdType="pubmed">6704173</ArticleId></ArticleIdList></Reference><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):22-5</Citation><ArticleIdList><ArticleId IdType="pubmed">20057045</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5717-22</Citation><ArticleIdList><ArticleId IdType="pubmed">16581910</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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