Identification of some dietary flavonoids as potential inhibitors of TMPRSS2 through protein–ligand interaction studies and binding free energy calculations

Abstract

The continuing threat of COVID-19 and deaths need an urgent cost-effective pharmacological approach. Here, we examine the inhibitory activity of a group of dietary bioactive flavonoids against the human protease TMPRSS2, which plays a major role in SARS CoV-2 viral entry. After the molecular docking studies of a large number of flavonoids, four compounds with high binding scores were selected and studied in detail. The binding affinities of these four ligands, Amentoflavone, Narirutin, Eriocitrin, and Naringin, at the active site of the TMPRSS2 target, were investigated using MD simulations followed by MM-PBSA binding energy calculations. From the studies, a number of significant hydrophobic and hydrogen bonding interactions between the ligands and binding site amino residues of TMPRSS2 are identified which showcase their excellent inhibitory activity against TMPRSS2. Among these ligands, Amentoflavone and Narirutin showed MM-PBSA binding energy values of −155.57 and −139.71 kJ/mol, respectively. Our previous studies of the inhibitory activity of these compounds against the main protease of SARS-COV2 and the present study on TMPRSS2 strongly highlighted that Amentoflavone and Naringin can exhibit promising multi-target activity against SARS-CoV-2. Moreover, due to their wide availability, no side effects, and low cost, these compounds could be recommended as dietary supplements for COVID patients or for the development of SARS-CoV-2 treatments. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-01955-7.

Comparison of DASH diet score and total antioxidant capacity of diet on serum levels of TMPRSS‐2, inflammatory biomarkers, and disease severity in COVID‐19 patients: A case–control study

“…Alternatively, it may be worth exploring the potential association between a diet high in flavonoids and TMPRSS‐2, as previous studies have demonstrated the anti‐SARS‐CoV‐2 activity of various flavonoids, including hesperidin, amentoflavone, and narirutin. These flavonoids have shown the ability to bind to the active site of the TMPRSS‐2 protein, inhibiting its activity through hydrophobic and hydrogen bond interactions (Bellavite & Donzelli, 2020 ; Haggag et al., 2020 ; Varughese & Francis, 2022 ). However, in the present study, no significant relationship was discovered between dietary pattern scores and TMPRSS‐2.…”

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

“…Molecular docking analysis has predicted that small molecules have a functional inhibitory effect on TMPRSS2 [ 21 ]. Many dietary flavonoids show promising multitarget activities against SARS-CoV-2 [ 35 ]. A small-molecule compound, N-0385, has recently been reported to act as a pan-SARS-CoV-2 prophylactic and therapeutic agent with TMPRSS2 inhibitory activity [ 36 ].…”