Docking simulations exhibit bortezomib and other boron-con-taining peptidomimetics as potential inhibitors of sars-cov-2 main protease

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Treatment of the COVID19 pandemic requires drug de-velopment. 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 li-gands. These advances may be relevant to drug designing, in addition to testing available boron-containing drugs in patients with COVID19 infection.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalCurrent Chemical Biology
Volume14
Issue number4
DOIs
StatePublished - 2020

Keywords

  • Boron
  • Boronic acids
  • Bortezomib
  • COVID19
  • Oligopeptides
  • Protease inhibitors

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