Title:Docking Simulations Exhibit Bortezomib and other Boron-containing Peptidomimetics as Potential Inhibitors of SARS-CoV-2 Main Protease
VOLUME: 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.*
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
Keywords:Boron, boronic acids, oligopeptides, bortezomib, protease inhibitors, COVID19.
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.
