Discovery of a Novel Family of SARS-CoV Protease Inhibitors by Virtual Screening and 3D-QSAR Studies

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3C-like protease (3CLpro or Mpro) is an attractive target for the development of anti-SARS drugs because of its crucial role in the viral life cycle. In this study, a compound database was screened by the structure-based virtual...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of medicinal chemistry 2006-06, Vol.49 (12), p.3485-3495
Hauptverfasser: Tsai, Keng-Chang, Chen, Shih-Yuan, Liang, Po-Huang, Lu, I-Lin, Mahindroo, Neeraj, Hsieh, Hsing-Pang, Chao, Yu-Sheng, Liu, Lincoln, Liu, Donald, Lien, Wei, Lin, Thy-Hou, Wu, Su-Ying
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3C-like protease (3CLpro or Mpro) is an attractive target for the development of anti-SARS drugs because of its crucial role in the viral life cycle. In this study, a compound database was screened by the structure-based virtual screening approach to identify initial hits as inhibitors of SARS-CoV 3CLpro. Out of the 59 363 compounds docked, 93 were selected for the inhibition assay, and 21 showed inhibition against SARS-CoV 3CLpro (IC50 ≤ 30 μM), with three of them having common substructures. Furthermore, a search for analogues with common substructure in the Maybridge, ChemBridge, and SPECS_SC databases led to the identification of another 25 compounds that exhibited inhibition against SARS-CoV 3CLpro (IC50 = 3−1000 μM). These compounds, 28 in total, were subjected to 3D-QSAR studies to elucidate the pharmacophore of SARS-CoV 3CLpro.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm050852f