Design, synthesis and docking study of Vortioxetine derivatives as a SARS-CoV-2 main protease inhibitor

Daru. 2022 Jun;30(1):139-152. doi: 10.1007/s40199-022-00441-z. Epub 2022 May 4.

Abstract

Purpose: Vortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2.

Methods: In this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (Mpro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper.

Results: Based on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards Mpro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 Mpro) and vortioxetine.

Conclusion: This study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment.

Keywords: Main protease; Remdesivir; SARS-CoV-2; Vortioxetine.

MeSH terms

  • Antiviral Agents / pharmacology
  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2*
  • Vortioxetine / pharmacology

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • Vortioxetine
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases