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

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 and 3m could inhibit both NA and 3CL pro and serve as a starting point to develop broad-spectrum antiviral agents.