Docking Simulations Exhibit Bortezomib and other Boron-containing Peptidomimetics as Potential Inhibitors of SARS-CoV-2 Main Protease

Abstract

Treatment of the COVID19 pandemic requires drug development. Boron- containing compounds are attractive chemical agents, some of them act as proteases inhibitors. The present study explores the role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. Conventional docking procedure was applied by assaying boron-free and boron-containing compounds on the recently reported crystal structure of SARS-CoV-2 main protease (PDB code: 6LU7). The set of 150 ligands includes bortezomib and inhibitors of coronavirus proteases. Most of the tested compounds share contact with key residues and pose on the cleavage pocket. The compounds with a boron atom in their structure are often estimated to have higher affinity than boron-free analogues. Interactions and the affinity of boron-containing peptidomimetics strongly suggest that boron-moieties increase affinity on the main protease, which is tested by in vitro assays. A Bis-boron-containing compound previously tested active on SARS-virus protease and bortezomib were identified as potent ligands. These advances may be relevant to drug designing, in addition to testing available boron-containing drugs in patients with COVID19 infection.