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

Vega-Valdez, Iván R.; Melvin N, Rosalez José M Santiago-Quintana D Farfán-García E.; Marvin A, Soriano-Ursúa

Background: Treatment of the COVID19 pandemic requires drug development. Boron- containing compounds are attractive chemical agents, some of them act as proteases inhibitors. Objective: The present study explores the role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. Methods: 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. Results: 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. Conclusion: 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.