Abstract
SARS is a viral respiratory illness caused by a previously unrecognized coronavirus, called SARS-associated coronavirus (SARS-CoV). Because of the potential for a rapid spread of the disease, it is vitally important to identify drugs that effectively inhibit a known target of the SARS coronavirus. Because of its essential role in proteolytic processing, the main protease MPro, a cysteine protease, is considered an attractive target for antiviral drugs against SARS and other coronavirus infections. In this review, we will present both peptidic and non-peptidic inhibitors that have been designed against SARS MPro. The most challenging requirement in designing cysteine inhibitors is to obtain a selective non-covalent electrophilic isostere that can react with the catalytic nucleophile. Emphasis will be put on our recent results, both experimental and theoretical, in the search for potent wide-spectrum inhibitors. The antiviral activity of the octopeptide AVLQSGFR against SARS-associated coronavirus will be presented as well as the recent hits obtained from virtual high throughput screening (vHTS) based on the identification of six hydrogen bond pharmacophore points from KZ7088 docked into the active site of SARS MPro.
Keywords: SARS, severe acute respiratory syndrome, coronavirus main proteinase, KZ7088, pharmacophore search, binding pocket, computer-assisted drug design, docking, virtual screening
Current Computer-Aided Drug Design
Title: Discovery of Potent Anti-SARS-CoV MPro Inhibitors
Volume: 3 Issue: 3
Author(s): Suzanne Sirois, Rui Zhang, Weina Gao, Hui Gao, Yun Li, Huiqin Zheng and Dong-Qing Wei
Affiliation:
Keywords: SARS, severe acute respiratory syndrome, coronavirus main proteinase, KZ7088, pharmacophore search, binding pocket, computer-assisted drug design, docking, virtual screening
Abstract: SARS is a viral respiratory illness caused by a previously unrecognized coronavirus, called SARS-associated coronavirus (SARS-CoV). Because of the potential for a rapid spread of the disease, it is vitally important to identify drugs that effectively inhibit a known target of the SARS coronavirus. Because of its essential role in proteolytic processing, the main protease MPro, a cysteine protease, is considered an attractive target for antiviral drugs against SARS and other coronavirus infections. In this review, we will present both peptidic and non-peptidic inhibitors that have been designed against SARS MPro. The most challenging requirement in designing cysteine inhibitors is to obtain a selective non-covalent electrophilic isostere that can react with the catalytic nucleophile. Emphasis will be put on our recent results, both experimental and theoretical, in the search for potent wide-spectrum inhibitors. The antiviral activity of the octopeptide AVLQSGFR against SARS-associated coronavirus will be presented as well as the recent hits obtained from virtual high throughput screening (vHTS) based on the identification of six hydrogen bond pharmacophore points from KZ7088 docked into the active site of SARS MPro.
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Cite this article as:
Sirois Suzanne, Zhang Rui, Gao Weina, Gao Hui, Li Yun, Zheng Huiqin and Wei Dong-Qing, Discovery of Potent Anti-SARS-CoV MPro Inhibitors, Current Computer-Aided Drug Design 2007; 3 (3) . https://dx.doi.org/10.2174/157340907781695440
DOI https://dx.doi.org/10.2174/157340907781695440 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
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