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 the tribuloside, legalon and isosilybin compounds should be evaluated in future studies to determine their efficacy to inhibit SARS-CoV-2 infectivity.
- Molecular dynamics (MD)
- binding free energy