Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: Homology modelling and molecular dynamic studies

Abstract

The coronavirus 3 chymotrypsin-like protease (3CLpro) is a validated target in the design of potential anticoronavirus inhibitors. The high degree of homology within the protease’s active site and substrate conservation supports the identification of broad spectrum lead compounds. A previous study identified the compound ML188, also termed 16R, as an inhibitor of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) 3CLpro. This study will detail the generation of a homology model of the 3CLpro of the human coronavirus OC43 and determine the potential of 16R to form a broad-spectrum lead compound. MODELLER was used to generate a suitable three-dimensional model of the OC43 3CLpro and the Prime module of Schrӧdinger predicted the binding conformation and free energy of binding of 16R within the 3CLpro active site. Molecular dynamics further confirmed ligand stability and hydrogen bonding networks.