Molecular docking and dynamics study to explore phytochemical ligand molecules against the main protease of SARS-CoV-2 from extensive phytochemical datasets

Expert Rev Clin Pharmacol. 2021 Oct;14(10):1305-1315. doi: 10.1080/17512433.2021.1959318. Epub 2021 Aug 5.

Abstract

Background: The high transmission and pathogenicity of SARS-CoV-2 has led to a pandemic that has halted the world's economy and health. The newly evolved strains and scarcity of vaccines has worsened the situation. The main protease (Mpro) of SARS-CoV-2 can act as a potential target due to its role in viral replication and conservation level.

Methods: In this study, we have enlisted more than 1100 phytochemicals from Asian plants based on deep literature mining. The compounds library was screened against the Mpro of SARS-CoV-2.

Results: The selected three ligands, Flemichin, Delta-Oleanolic acid, and Emodin 1-O-beta-D-glucoside had a binding energy of -8.9, -8.9, -8.7 KJ/mol respectively. The compounds bind to the active groove of the main protease at; Cys145, Glu166, His41, Met49, Pro168, Met165, Gln189. The multiple descriptors from the simulation study; root mean square deviation, root mean square fluctuation, radius of gyration, hydrogen bond, solvent accessible surface area confirms the stable nature of the protein-ligand complexes. Furthermore, post-md analysis confirms the rigidness in the docked poses over the simulation trajectories.

Conclusions: Our combinatorial drug design approaches may help researchers to identify suitable drug candidates against SARS-CoV-2.

Keywords: SARS-CoV-2; admet; molecular docking; molecular dynamics; phytochemicals.

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Databases, Chemical
  • Drug Discovery*
  • Gene Expression Regulation, Viral / drug effects
  • Molecular Docking Simulation
  • Molecular Structure
  • Phytochemicals / chemistry
  • Phytochemicals / pharmacology*
  • SARS-CoV-2 / enzymology*
  • Viral Proteases / genetics
  • Viral Proteases / metabolism*

Substances

  • Antiviral Agents
  • Phytochemicals
  • Viral Proteases