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

[ Vol. 14 , Issue. 4 ]

Author(s):

Iván R Vega-Valdez, Rosalez Melvin N., Santiago-Quintana José M., Farfán-García Eunice D. and Soriano-Ursúa Marvin A.*   Pages 279 - 288 ( 10 )

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 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.

Keywords:

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

Affiliation:

Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, Mexico City, 11340, Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, Mexico City, 11340, Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, Mexico City, 11340, Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, Mexico City, 11340, Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron s/n, Mexico City, 11340

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