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
Highlights
The pandemic outbreak of the novel Coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the respiratory illness and named as coronavirus disease-2019 (COVID-19) worldwide [1]
To reduce the chemical space, the threshold glide score, Autodock vina (ADV) binding energy and Prime-MMGBSA binding free energy molecules was explored after docking through ADV
Five promising molecules were obtained through structure-based virtual screening for Transmembrane protease serine-2 (TMPRSS2) inhibition
Summary
The pandemic outbreak of the novel Coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the respiratory illness and named as coronavirus disease-2019 (COVID-19) worldwide [1]. This deadly disease left millions of human being infected and thousands of deaths [2]. The availability of experimental drug targets associated with COVID-19 is the key for clinical/biologic evaluations of drug efficacies, investigations of therapeutic mechanisms and searches of drug-repurposing opportunities [7, 8]
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