Virtual screening of thiazole-based heterocyclic derivatives as inhibitors of Coronavirus 3CLpro enzymes for the development of COVID-19 therapeutics

The enzyme 3-chymotrypsin-like protease (3CLpro) of Coronavirus plays a crucial role in viral replication and is a validated target in the development of new drugs for the treatment of COVID-19.However, till now, most reported 3CLpro inhibitors are raising concerns regarding drug resistance, low efficacy when used as monotherapy.On the other hand, the thiazole scaffold is a privileged structure with potential biological activities.With the aim of finding compounds that can inhibit new 3CLpro enzymatic activity, we applied molecular docking simulations to investigate the interactions between 40 thiazole-based derivatives, including small molecules and Food and Drug Administration (FDA) -approved drugs, with the 3CLpro enzymes of SARS-CoV, MERS-CoV, and particularly SARS-CoV-2.The simulation results revealed that 8 potential compounds are capable of binding directly to the catalytic site of 3CLpro, including edoxaban, ixabepilone, dabrafenib, and ceftaroline fosamil, which exhibited binding affinities to SARS-CoV-2 3CLpro of -8.6, -8.7, -8.8, and -8.9 kcal/mol, respectively.This study presents a reliable in silico screening model for the identification of novel 3CLpro inhibitors bearing thiazole scaffolds, contributing to the development of potential antiviral drugs against SARS-CoV-2.