Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies

Keng-Chang Tsai, Shih-Yuan Chen, Po-Huang Liang, I-Lin Lu, Neeraj Mahindroo, Hsing-Pang Hsieh, Yu-Sheng Chao, Lincoln Liu, Donald Liu, Wei Lien, Thy-Hou Lin, Su-Ying Wu
Journal of Medicinal Chemistry 2006 June 15, 49 (12): 3485-95
The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3C-like protease (3CL(pro) or M(pro)) 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 3CL(pro). Out of the 59,363 compounds docked, 93 were selected for the inhibition assay, and 21 showed inhibition against SARS-CoV 3CL(pro) (IC(50) <or= 30 microM), 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 3CL(pro) (IC(50) = 3-1,000 microM). These compounds, 28 in total, were subjected to 3D-QSAR studies to elucidate the pharmacophore of SARS-CoV 3CL(pro).

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"