No 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.

The global spread of the COVID-19 pandemic caused by the etiological agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), triggered researchers to identify and develop novel antiviral therapeutics. Herein, we report a new molecule 2-hydroxy-1,2-diphenylethanone N(4)-methyl-N(4)-phenyl thiosemicarbazone (BMPTSC), as a potential inhibitor of SARS-CoV-2. BMPTSC was synthesized, characterized by IR and NMR studies, and the structural parameters were analyzed computationally by B3LYP/cc-pVDZ method. Molecular docking studies were performed to get insights into the energetics and compatibility of BMPTSC against various SARS-CoV-2 drug targets. The best docking poses of target protein-BMPTSC complex structures were further subjected to molecular dynamics (MD) simulations. Molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations on the binding of BMPTSC with the target proteins viz. spike glycoprotein and ACE-2 protein showed energy values of −179.87 and −145.61 kJ/mol, respectively. Moreover, BMPTSC obeys Lipinski’s rule, and further in silico assessment of oral bioavailability, bioactivity scores, ADME, drug-likeness, and medicinal chemistry friendliness suggests that this molecule is a promising candidate for the COVID-19 drug discovery process. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-02033-8.

The alarming increase in COVID-19 cases and deaths calls for 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 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 -155.48 and -138.13 kJ/mol respectively. Our previous studies of the inhibitory activity of these compounds against 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.