Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.
Identifieur interne : 005718 ( Main/Merge ); précédent : 005717; suivant : 005719Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.
Auteurs : Richard Y. Kao [République populaire de Chine] ; Wayne H W. Tsui ; Terri S W. Lee ; Julian A. Tanner ; Rory M. Watt ; Jian-Dong Huang ; Lihong Hu ; Guanhua Chen ; Zhiwei Chen ; Linqi Zhang ; Tian He ; Kwok-Hung Chan ; Herman Tse ; Amanda P C. To ; Louisa W Y. Ng ; Bonnie C W. Wong ; Hoi-Wah Tsoi ; Dan Yang ; David D. Ho ; Kwok-Yung YuenSource :
- Chemistry & biology [ 1074-5521 ] ; 2004.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (), Antiviraux (pharmacologie), Antiviraux (synthèse chimique), Carboxypeptidases (antagonistes et inhibiteurs), Carboxypeptidases (métabolisme), Cellules Vero, Modèles moléculaires, Peptidyl-Dipeptidase A, Protéines de la matrice virale (antagonistes et inhibiteurs), Protéines de la matrice virale (métabolisme), Réplication virale (), Structure moléculaire, Syndrome respiratoire aigu sévère (traitement médicamenteux), Techniques de chimie combinatoire, Virus du SRAS (), Virus du SRAS (croissance et développement), Virus du SRAS (métabolisme), Virus du SRAS (physiologie).
- MESH :
- antagonistes et inhibiteurs : Carboxypeptidases, Protéines de la matrice virale.
- croissance et développement : Virus du SRAS.
- métabolisme : Carboxypeptidases, Protéines de la matrice virale, Virus du SRAS.
- pharmacologie : Antiviraux.
- physiologie : Virus du SRAS.
- synthèse chimique : Antiviraux.
- traitement médicamenteux : Syndrome respiratoire aigu sévère.
- Animaux, Antiviraux, Cellules Vero, Modèles moléculaires, Peptidyl-Dipeptidase A, Réplication virale, Structure moléculaire, Techniques de chimie combinatoire, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Carboxypeptidases (antagonists & inhibitors), Carboxypeptidases (metabolism), Chlorocebus aethiops, Combinatorial Chemistry Techniques, Models, Molecular, Molecular Structure, Peptidyl-Dipeptidase A, SARS Virus (drug effects), SARS Virus (growth & development), SARS Virus (metabolism), SARS Virus (physiology), Severe Acute Respiratory Syndrome (drug therapy), Vero Cells, Viral Matrix Proteins (antagonists & inhibitors), Viral Matrix Proteins (metabolism), Virus Replication (drug effects).
- MESH :
- chemical , antagonists & inhibitors : Carboxypeptidases, Viral Matrix Proteins.
- chemical , chemical synthesis : Antiviral Agents.
- chemical , chemistry : Antiviral Agents.
- chemical , metabolism : Carboxypeptidases, Viral Matrix Proteins.
- chemical , pharmacology : Antiviral Agents.
- drug effects : SARS Virus, Virus Replication.
- drug therapy : Severe Acute Respiratory Syndrome.
- growth & development : SARS Virus.
- metabolism : SARS Virus.
- physiology : SARS Virus.
- Animals, Chlorocebus aethiops, Combinatorial Chemistry Techniques, Models, Molecular, Molecular Structure, Peptidyl-Dipeptidase A, Vero Cells.
Abstract
The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (M(pro)), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC(50) of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV M(pro), Hel, and viral entry, respectively, exhibited potent antiviral activity (EC(50) < 10 microM) and comparable inhibitory activities in target-specific in vitro assays.
DOI: 10.1016/j.chembiol.2004.07.013
PubMed: 15380189
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pubmed:15380189Le document en format XML
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Ho</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2004">2004</date><idno type="RBID">pubmed:15380189</idno><idno type="pmid">15380189</idno><idno type="doi">10.1016/j.chembiol.2004.07.013</idno><idno type="wicri:Area/PubMed/Corpus">002B48</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002B48</idno><idno type="wicri:Area/PubMed/Curation">002B48</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002B48</idno><idno type="wicri:Area/PubMed/Checkpoint">002C60</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002C60</idno><idno type="wicri:Area/Ncbi/Merge">000A80</idno><idno type="wicri:Area/Ncbi/Curation">000A80</idno><idno type="wicri:Area/Ncbi/Checkpoint">000A80</idno><idno type="wicri:doubleKey">1074-5521:2004:Kao R:identification:of:novel</idno><idno type="wicri:Area/Main/Merge">005718</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.</title><author><name sortKey="Kao, Richard Y" sort="Kao, Richard Y" uniqKey="Kao R" first="Richard Y" last="Kao">Richard Y. Kao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. ryykao@hkucc.hku.hk</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Tsui, Wayne H W" sort="Tsui, Wayne H W" uniqKey="Tsui W" first="Wayne H W" last="Tsui">Wayne H W. Tsui</name></author><author><name sortKey="Lee, Terri S W" sort="Lee, Terri S W" uniqKey="Lee T" first="Terri S W" last="Lee">Terri S W. Lee</name></author><author><name sortKey="Tanner, Julian A" sort="Tanner, Julian A" uniqKey="Tanner J" first="Julian A" last="Tanner">Julian A. Tanner</name></author><author><name sortKey="Watt, Rory M" sort="Watt, Rory M" uniqKey="Watt R" first="Rory M" last="Watt">Rory M. Watt</name></author><author><name sortKey="Huang, Jian Dong" sort="Huang, Jian Dong" uniqKey="Huang J" first="Jian-Dong" last="Huang">Jian-Dong Huang</name></author><author><name sortKey="Hu, Lihong" sort="Hu, Lihong" uniqKey="Hu L" first="Lihong" last="Hu">Lihong Hu</name></author><author><name sortKey="Chen, Guanhua" sort="Chen, Guanhua" uniqKey="Chen G" first="Guanhua" last="Chen">Guanhua Chen</name></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name></author><author><name sortKey="He, Tian" sort="He, Tian" uniqKey="He T" first="Tian" last="He">Tian He</name></author><author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name></author><author><name sortKey="Tse, Herman" sort="Tse, Herman" uniqKey="Tse H" first="Herman" last="Tse">Herman Tse</name></author><author><name sortKey="To, Amanda P C" sort="To, Amanda P C" uniqKey="To A" first="Amanda P C" last="To">Amanda P C. To</name></author><author><name sortKey="Ng, Louisa W Y" sort="Ng, Louisa W Y" uniqKey="Ng L" first="Louisa W Y" last="Ng">Louisa W Y. Ng</name></author><author><name sortKey="Wong, Bonnie C W" sort="Wong, Bonnie C W" uniqKey="Wong B" first="Bonnie C W" last="Wong">Bonnie C W. Wong</name></author><author><name sortKey="Tsoi, Hoi Wah" sort="Tsoi, Hoi Wah" uniqKey="Tsoi H" first="Hoi-Wah" last="Tsoi">Hoi-Wah Tsoi</name></author><author><name sortKey="Yang, Dan" sort="Yang, Dan" uniqKey="Yang D" first="Dan" last="Yang">Dan Yang</name></author><author><name sortKey="Ho, David D" sort="Ho, David D" uniqKey="Ho D" first="David D" last="Ho">David D. Ho</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author></analytic><series><title level="j">Chemistry & biology</title><idno type="ISSN">1074-5521</idno><imprint><date when="2004" type="published">2004</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 (chemistry)</term><term>Antiviral Agents (pharmacology)</term><term>Carboxypeptidases (antagonists & inhibitors)</term><term>Carboxypeptidases (metabolism)</term><term>Chlorocebus aethiops</term><term>Combinatorial Chemistry Techniques</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Peptidyl-Dipeptidase A</term><term>SARS Virus (drug effects)</term><term>SARS Virus (growth & development)</term><term>SARS Virus (metabolism)</term><term>SARS Virus (physiology)</term><term>Severe Acute Respiratory Syndrome (drug therapy)</term><term>Vero Cells</term><term>Viral Matrix Proteins (antagonists & inhibitors)</term><term>Viral Matrix Proteins (metabolism)</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux ()</term><term>Antiviraux (pharmacologie)</term><term>Antiviraux (synthèse chimique)</term><term>Carboxypeptidases (antagonistes et inhibiteurs)</term><term>Carboxypeptidases (métabolisme)</term><term>Cellules Vero</term><term>Modèles moléculaires</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de la matrice virale (antagonistes et inhibiteurs)</term><term>Protéines de la matrice virale (métabolisme)</term><term>Réplication virale ()</term><term>Structure moléculaire</term><term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term><term>Techniques de chimie combinatoire</term><term>Virus du SRAS ()</term><term>Virus du SRAS (croissance et développement)</term><term>Virus du SRAS (métabolisme)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Carboxypeptidases</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carboxypeptidases</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Carboxypeptidases</term><term>Protéines de la matrice virale</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carboxypeptidases</term><term>Protéines de la matrice virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Combinatorial Chemistry Techniques</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Peptidyl-Dipeptidase A</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antiviraux</term><term>Cellules Vero</term><term>Modèles moléculaires</term><term>Peptidyl-Dipeptidase A</term><term>Réplication virale</term><term>Structure moléculaire</term><term>Techniques de chimie combinatoire</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (M(pro)), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC(50) of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV M(pro), Hel, and viral entry, respectively, exhibited potent antiviral activity (EC(50) < 10 microM) and comparable inhibitory activities in target-specific in vitro assays.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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