Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors. Issue 13 (1st July 2016)

• Record Type: Journal Article
• Authors: Kumar, Vathan; Tan, Kian-Pin; Wang, Ying-Ming; Lin, Sheng-Wei; Liang, Po-Huang
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 13(2016)
• Page Start: 3035
• Page End: 3042
• Publication Date: 2016-07-01
• Subjects: MERS-CoV -- SARS-Cov -- 3CLpro -- Coronavirus -- Pyrazolone; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.05.013
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 R 1 or R 4 destabilizes the oxyanion hole in the 3CL pro . Interestingly, 3f, 3g and3m could inhibit both NA and 3CL pro and serve as a starting point to develop broad-spectrum antiviral agents.