SrasV1, PubMed, Corpus, bibRecord, 002B48

Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.

Identifieur interne : 002B48 ( PubMed/Corpus ); précédent : 002B47; suivant : 002B49

Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.

Auteurs : Richard Y. Kao ; 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 Yuen

Source :

Chemistry & biology [ 1074-5521 ] ; 2004.

RBID : pubmed:15380189

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

Links to Exploration step

pubmed:15380189

Le document en format XML

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<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>
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<Abstract><AbstractText>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.</AbstractText>
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Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.

Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.

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