Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors.
Identifieur interne : 001056 ( Main/Exploration ); précédent : 001055; suivant : 001057Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors.
Auteurs : Fenghua Wang [République populaire de Chine] ; Cheng Chen [République populaire de Chine] ; Xuemeng Liu [République populaire de Chine] ; Kailin Yang [États-Unis] ; Xiaoling Xu [République populaire de Chine] ; Haitao Yang [République populaire de Chine]Source :
- Journal of virology [ 1098-5514 ] ; 2016.
Descripteurs français
- KwdFr :
- Conformation des protéines, Coronavirus félin (enzymologie), Cristallographie aux rayons X, Cysteine endopeptidases (), Cysteine endopeptidases (métabolisme), Données de séquences moléculaires, Inhibiteurs de protéases (), Inhibiteurs de protéases (métabolisme), Liaison aux protéines, Modèles moléculaires, Séquence d'acides aminés, Zinc (), Zinc (métabolisme).
- MESH :
- enzymologie : Coronavirus félin.
- métabolisme : Cysteine endopeptidases, Inhibiteurs de protéases, Zinc.
- Conformation des protéines, Cristallographie aux rayons X, Cysteine endopeptidases, Données de séquences moléculaires, Inhibiteurs de protéases, Liaison aux protéines, Modèles moléculaires, Séquence d'acides aminés, Zinc.
English descriptors
- KwdEn :
- Amino Acid Sequence, Coronavirus, Feline (enzymology), Crystallography, X-Ray, Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (metabolism), Models, Molecular, Molecular Sequence Data, Protease Inhibitors (chemistry), Protease Inhibitors (metabolism), Protein Binding, Protein Conformation, Zinc (chemistry), Zinc (metabolism).
- MESH :
- chemical , chemistry : Cysteine Endopeptidases, Protease Inhibitors, Zinc.
- enzymology : Coronavirus, Feline.
- chemical , metabolism : Cysteine Endopeptidases, Protease Inhibitors, Zinc.
- Amino Acid Sequence, Crystallography, X-Ray, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation.
Abstract
Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases.
DOI: 10.1128/JVI.02685-15
PubMed: 26656689
Affiliations:
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Le document en format XML
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<term>Cysteine Endopeptidases (chemistry)</term>
<term>Cysteine Endopeptidases (metabolism)</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Protease Inhibitors (chemistry)</term>
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<term>Cysteine endopeptidases (métabolisme)</term>
<term>Données de séquences moléculaires</term>
<term>Inhibiteurs de protéases ()</term>
<term>Inhibiteurs de protéases (métabolisme)</term>
<term>Liaison aux protéines</term>
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<term>Zinc</term>
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<term>Protease Inhibitors</term>
<term>Zinc</term>
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<term>Données de séquences moléculaires</term>
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<front><div type="abstract" xml:lang="en">Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases.</div>
</front>
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