From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design
Identifieur interne : 001C50 ( Main/Exploration ); précédent : 001C49; suivant : 001C51From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design
Auteurs : Rolf HilgenfeldSource :
- The Febs Journal [ 1742-464X ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : Antiviral Agents, Peptide Hydrolases, Protease Inhibitors, Viral Proteins.
- enzymology : SARS Virus.
- Animals, Crystallography, X-Ray, Drug Design, Humans, Models, Molecular, Molecular Targeted Therapy.
Abstract
This review focuses on the important contributions that macromolecular crystallography has made over the past 12 years to elucidating structures and mechanisms of the essential proteases of coronaviruses, the main protease (Mpro) and the papain‐like protease (PLpro). The role of X‐ray crystallography in structure‐assisted drug discovery against these targets is discussed. Aspects dealt with in this review include the emergence of the SARS coronavirus in 2002–2003 and of the
Url:
DOI: 10.1111/febs.12936
PubMed: 25039866
PubMed Central: 7163996
Affiliations:
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Le document en format XML
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type="wicri:Area/Main/Curation">001C50</idno><idno type="wicri:Area/Main/Exploration">001C50</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">From <styled-content style="fixed-case" toggle="no">SARS</styled-content> to <styled-content style="fixed-case" toggle="no">MERS</styled-content>: crystallographic studies on coronaviral proteases enable antiviral drug design</title><author><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name><affiliation><nlm:aff id="febs12936-aff-0001"></nlm:aff></affiliation></author></analytic><series><title level="j">The Febs Journal</title><idno type="ISSN">1742-464X</idno><idno type="eISSN">1742-4658</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (chemistry)</term><term>Crystallography, X-Ray</term><term>Drug Design</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Targeted Therapy</term><term>Peptide Hydrolases (chemistry)</term><term>Protease Inhibitors (chemistry)</term><term>SARS Virus (enzymology)</term><term>Viral Proteins (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux ()</term><term>Conception de médicament</term><term>Cristallographie aux rayons X</term><term>Humains</term><term>Inhibiteurs de protéases ()</term><term>Modèles moléculaires</term><term>Peptide hydrolases ()</term><term>Protéines virales ()</term><term>Thérapie moléculaire ciblée</term><term>Virus du SRAS (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Peptide Hydrolases</term><term>Protease Inhibitors</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Crystallography, X-Ray</term><term>Drug Design</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Targeted Therapy</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antiviraux</term><term>Conception de médicament</term><term>Cristallographie aux rayons X</term><term>Humains</term><term>Inhibiteurs de protéases</term><term>Modèles moléculaires</term><term>Peptide hydrolases</term><term>Protéines virales</term><term>Thérapie moléculaire ciblée</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>This review focuses on the important contributions that macromolecular crystallography has made over the past 12 years to elucidating structures and mechanisms of the essential proteases of coronaviruses, the main protease (M<sup>pro</sup>) and the papain‐like protease (PL<sup>pro</sup>). The role of X‐ray crystallography in structure‐assisted drug discovery against these targets is discussed. Aspects dealt with in this review include the emergence of the SARS coronavirus in 2002–2003 and of the <styled-content style="fixed-case" toggle="no">MERS</styled-content> coronavirus 10 years later and the origins of these viruses. The crystal structure of the free SARS coronavirus M<sup>pro</sup> and its dependence on pH is discussed, as are efforts to design inhibitors on the basis of these structures. The mechanism of maturation of the enzyme from the viral polyprotein is still a matter of debate. The crystal structure of the SARS coronavirus PL<sup>pro</sup> and its complex with ubiquitin is also discussed, as is its orthologue from <styled-content style="fixed-case" toggle="no">MERS</styled-content> coronavirus. Efforts at predictive structure‐based inhibitor development for bat coronavirus M<sup>pro</sup>s to increase the preparedness against zoonotic transmission to man are described as well. The paper closes with a brief discussion of structure‐based discovery of antivirals in an academic setting.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Sussman, J" uniqKey="Sussman J">J Sussman</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Schmidt, A" uniqKey="Schmidt A">A Schmidt</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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