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

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Author(s): Iván R Vega-Valdez, Melvin N Rosalez, José M Santiago-Quintana, Eunice D Farfán-García, Marvin A Soriano-Ursúa*

Journal Name: Current Chemical Biology

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Abstract:

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 poses on the cleavage pocket. Those compounds with a boron atom in its structure were often estimated with higher affinity than boron-free analogues.

Conclusion: Interactions and the affinity of boron-containing peptidomimetics strongly suggest boron-moieties increases affinity on the main protease, as it should be tested by in vitro assays. A Bis-boron-containing compound previously tested as active on SARS-virus protease and bortezomib were identified as potent ligands. These advances may be relevant for drug designing, in addition as to the suggestion of testing available boron-containing drugs in patients with COVID19 infection.

Keywords: Boron, boronic acids, oligopeptides, bortezomib, protease inhibitors, COVID19.

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