Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors

Shakya, Anshul; Chikhale, Rupesh V.; Bhat, Hans Raj; Alasmary, Fatmah Ali; Almutairi, Tahani Mazyad; Ghosh, Surajit Kumar; Alhajri, Hassna Mohammed; Alissa, Siham A.; Nagar, Shuchi; Islam, Md Ataul

ABSTRACT: Transmembrane protease serine-2 (TMPRSS2) is a cell-surface protein expressed by epithelial cells of specific tissues including those in the aerodigestive tract. It helps the entry of novel coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the host cell. Successful inhibition of the TMPRSS2 can be one of the crucial strategies to stop the SARS-CoV-2 infection. In the present study, a set of bioactive molecules from Morus alba Linn. were screened against the TMPRSS2 through two widely used molecular docking engines such as Autodock vina and Glide. Molecules having a higher binding affinity toward the TMPRSS2 compared to Camostat and Ambroxol were considered for in-silico pharmacokinetic analyses. Based on acceptable pharmacokinetic parameters and drug-likeness, finally, five molecules were found to be important for the TMPRSS2 inhibition. A number of bonding interactions in terms of hydrogen bond and hydrophobic interactions were observed between the proposed molecules and ligand-interacting amino acids of the TMPRSS2. The dynamic behavior and stability of best-docked complex between TRMPRSS2 and proposed molecules were assessed through molecular dynamics (MD) simulation. Several parameters from MD simulation have suggested the stability between the protein and ligands. Binding free energy of each molecule calculated through MM-GBSA approach from the MD simulation trajectory suggested strong affection toward the TMPRSS2. Hence, proposed molecules might be crucial chemical components for the TMPRSS2 inhibition. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-021-10209-3.