The interaction of the bioflavonoids with five SARS-CoV-2 proteins targets: An in silico study

Comput Biol Med. 2021 Jul:134:104464. doi: 10.1016/j.compbiomed.2021.104464. Epub 2021 May 10.

Abstract

Flavonoids have been shown to have antioxidant, anti-inflammatory, anti-proliferative, antibacterial and antiviral efficacy. Therefore, in this study, we choose 85 flavonoid compounds and screened them to determine their in-silico interaction with protein targets crucial for SARS-CoV-2 infection. The five important targets chosen were the main protease (Mpro), Spike receptor binding domain (Spike-RBD), RNA - dependent RNA polymerase (RdRp or Nsp12), non-structural protein 15 (Nsp15) of SARS-CoV-2 and the host angiotensin converting enzyme-2 (ACE-2) spike-RBD binding domain. The compounds were initially docked at the selected sites and further evaluated for binding free energy, using the molecular mechanics/generalized Born surface area (MMGBSA) method. The three compounds with the best binding scores were subjected to molecular dynamics (MD) simulations. The compound, tribuloside, had a high average binding free energy of -86.99 and -88.98 kcal/mol for Mpro and Nsp12, respectively. The compound, legalon, had an average binding free energy of -59.02 kcal/mol at the ACE2 spike-RBD binding site. The compound, isosilybin, had an average free binding energy of -63.06 kcal/mol for the Spike-RBD protein. Overall, our results suggest that tribuloside, legalon and isosilybin should be evaluated in future studies to determine their efficacy to inhibit SARS-CoV-2 infectivity.

Keywords: Binding free energy; Docking; Flavonoids; MMGBSA; Molecular dynamics (MD); SARS-CoV-2.

MeSH terms

  • COVID-19*
  • Flavonoids
  • Humans
  • Molecular Docking Simulation
  • Protein Binding
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus

Substances

  • Flavonoids
  • Spike Glycoprotein, Coronavirus