Bioorganic & Medicinal Chemistry
Volume 24, Issue 13, 1 July 2016, Pages 3035-3042
Vathan Kumar, Kian-Pin Tan, Ying-Ming Wang, Sheng-Wei Lin, Po-Huang Liang
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 3CLpro of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R1 or R4 destabilizes the oxyanion hole in the 3CLpro. Interestingly, 3f, 3g and 3m could inhibit both NA and 3CLpro and serve as a starting point to develop broad-spectrum antiviral agents.
Keywords
MERS-CoV, SARS-Cov, 3CLpro, Coronavirus, Pyrazolone