Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors

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• 作者：Vathan Kumar^a ; Kian-Pin Tan^b ; Ying-Ming Wang^a ; Sheng-Wei Lin^a ; Po-Huang Liang^a ; ^b ; ^{phliang@gate.sinica.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MERS-CoV ; SARS-Cov ; 3CLpro ; Coronavirus ; Pyrazolone
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：24
• 期：13
• 页码：3035-3042
• 全文大小：954 K

文摘

Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CL^pro of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R¹ or R⁴ destabilizes the oxyanion hole in the 3CL^pro. Interestingly, 3f, 3g and 3m could inhibit both NA and 3CL^pro and serve as a starting point to develop broad-spectrum antiviral agents.