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

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 the tribuloside, legalon and isosilybin compounds should be evaluated in future studies to determine their efficacy to inhibit SARS-CoV-2 infectivity.

Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication

“… 24 There was only marginal overlap between our enzymatic screening of flavonoid Mpro inhibitors and previous in silico screens. 22 Conversely, screens of small collections of flavonoids 43 , 44 or extracts of natural products 45 , 46 are far less inclusive and lack the extensive opportunity for SARs provided by enzymatic screening of a large flavonoid library. The finding that biflavones and galloylated flavonoids are enriched in Mpro inhibitors could help guide future identification and development of flavonoid-based treatments for COVID-19.…”

Targeting SARS-CoV-2 endoribonuclease: a structure-based virtual screening supported by in vitro analysis

“…Endoribonuclease (EndoU or NSP15) is a 346 residue protein with three domains namely, the N-terminal domain, middle domain, and the C-terminal domain. The N-terminal domain was found to be responsible for the formation of a hexamer, while the C-terminal domain contains the active site of the protein that facilitates replication and processing of sub-genomic RNAs 9 – 12 . It was found that NSP15 hydrolyzes the phosphodiester bond that is located at the uridine (U) sites of single and double-stranded RNA molecules.…”

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

“…The investigation of the binding power of the aforementioned compounds to the SARS-CoV-2 enzyme protease (6LU7) was conducted through the utilization of molecular docking strategy [ 39 , 40 ]. The generation of the three-dimensional models of the title compounds was done utilizing the builder user interface of MOE [ 41 ].…”