SrasV1, PubMed, Curation, bibRecord, 002B09

High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase.

Identifieur interne : 002B09 ( PubMed/Curation ); précédent : 002B08; suivant : 002B10

High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase.

Auteurs : Jan E. Blanchard [Canada] ; Nadine H. Elowe ; Carly Huitema ; Pascal D. Fortin ; Jonathan D. Cechetto ; Lindsay D. Eltis ; Eric D. Brown

Source :

Chemistry & biology [ 1074-5521 ] ; 2004.

RBID : pubmed:15489171

Descripteurs français

KwdFr :
- Animaux, Antiviraux (isolement et purification), Antiviraux (pharmacologie), Bovins, Cysteine endopeptidases, Endopeptidases (métabolisme), Inhibiteurs de protéases (), Inhibiteurs de protéases (isolement et purification), Inhibiteurs de protéases (pharmacologie), Protéines virales (antagonistes et inhibiteurs), Protéines virales (métabolisme), Spectrométrie de masse (), Virus du SRAS (), Virus du SRAS (enzymologie).
MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Virus du SRAS.
- isolement et purification : Antiviraux, Inhibiteurs de protéases.
- métabolisme : Endopeptidases, Protéines virales.
- pharmacologie : Antiviraux, Inhibiteurs de protéases.
- Animaux, Bovins, Cysteine endopeptidases, Inhibiteurs de protéases, Spectrométrie de masse, Virus du SRAS.

English descriptors

KwdEn :
- Animals, Antiviral Agents (isolation & purification), Antiviral Agents (pharmacology), Cattle, Cysteine Endopeptidases, Endopeptidases (metabolism), Mass Spectrometry (methods), Protease Inhibitors (chemistry), Protease Inhibitors (isolation & purification), Protease Inhibitors (pharmacology), SARS Virus (drug effects), SARS Virus (enzymology), Viral Proteins (antagonists & inhibitors), Viral Proteins (metabolism).
MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Protease Inhibitors.
- chemical , isolation & purification : Antiviral Agents, Protease Inhibitors.
- chemical , metabolism : Endopeptidases, Viral Proteins.
- chemical , pharmacology : Antiviral Agents, Protease Inhibitors.
- drug effects : SARS Virus.
- enzymology : SARS Virus.
- methods : Mass Spectrometry.
- Animals, Cattle, Cysteine Endopeptidases.

Abstract

The causative agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus, SARS-CoV. The main proteinase of SARS-CoV, 3CLpro, is an attractive target for therapeutics against SARS owing to its fundamental role in viral replication. We sought to identify novel inhibitors of 3CLpro to advance the development of appropriate therapies in the treatment of SARS. 3CLpro was cloned, expressed, and purified from the Tor2 isolate. A quenched fluorescence resonance energy transfer assay was developed for 3CLpro to screen the proteinase against 50,000 drug-like small molecules on a fully automated system. The primary screen identified 572 hits; through a series of virtual and experimental filters, this number was reduced to five novel small molecules that show potent inhibitory activity (IC50 = 0.5-7 microM) toward SARS-CoV 3CLpro.

DOI: 10.1016/j.chembiol.2004.08.011
PubMed: 15489171

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Le document en format XML

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<front><div type="abstract" xml:lang="en">The causative agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus, SARS-CoV. The main proteinase of SARS-CoV, 3CLpro, is an attractive target for therapeutics against SARS owing to its fundamental role in viral replication. We sought to identify novel inhibitors of 3CLpro to advance the development of appropriate therapies in the treatment of SARS. 3CLpro was cloned, expressed, and purified from the Tor2 isolate. A quenched fluorescence resonance energy transfer assay was developed for 3CLpro to screen the proteinase against 50,000 drug-like small molecules on a fully automated system. The primary screen identified 572 hits; through a series of virtual and experimental filters, this number was reduced to five novel small molecules that show potent inhibitory activity (IC50 = 0.5-7 microM) toward SARS-CoV 3CLpro.</div>
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High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase.

High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase.

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