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

doi:10.1021/jm050852f

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

Center of Applied Nanomedicine

Research output: Contribution to journal › Article › peer-review

58 Citations (Scopus)

Abstract

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 (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 3CL^pro (IC₅₀ = 3-1000 μM). These compounds, 28 in total, were subjected to 3D-QSAR studies to elucidate the pharmacophore of SARS-CoV 3CL^pro.

Original language	English
Pages (from-to)	3485-3495
Number of pages	11
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	12
DOIs	https://doi.org/10.1021/jm050852f
Publication status	Published - 2006 Jun 15

All Science Journal Classification (ASJC) codes

Molecular Medicine
Drug Discovery

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10.1021/jm050852f

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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. / Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 12. pp. 3485-3495.

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

abstract = "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.",

author = "Tsai, {Keng Chang} and Chen, {Shih Yuan} and Liang, {Po Huang} and Lu, {I. Lin} and Neeraj Mahindroo and Hsieh, {Hsing Pang} and Chao, {Yu Sheng} and Lincoln Liu and Donald Liu and Wei Lien and Lin, {Thy Hou} and Wu, {Su Ying}",

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

In: Journal of Medicinal Chemistry, Vol. 49, No. 12, 15.06.2006, p. 3485-3495.

Research output: Contribution to journal › Article › peer-review

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AU - Liu, Lincoln

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AU - Lien, Wei

AU - Lin, Thy Hou

AU - Wu, Su Ying

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

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