Molecular Docking Studies of Bioactive Constituents of Long Pepper, Ginger, Clove, and Black Pepper to Target the Human Cathepsin L Protease: As a Natural Therapeutic Strategy Against SARS-Cov-2

Abstract

Human cathepsin L protease is involved in the cleavage of S protein of SARS-Cov-2 virus and activates the membrane fusion, which mediates the entry of the virus into the host cell. Thus, it suggests the cathepsin L protease is critical for the entry of SARS-Cov-2. Currently, chemically synthesized cathepsin L inhibitors are present, but the consumption of chemically synthesized drugs is also an alarming stage due to its side effects, illness, and age reduction. In this study, natural bioactive constituents of long pepper, ginger, clove, and black pepper that has been widely known for antiviral effect and other medicinal properties were used for molecular docking against the human cathepsin L receptor (PDB ID 2XU1). Molecular docking (using a software, AutoDock 4.2) was performed on bioactive constituents of long pepper, ginger, clove, and black pepper against the human cathepsin L protease and elucidates the binding energies, visualization, and analysis of interacting residue (using Discovery studio) at the docking site of cathepsin L protease and compared the docking analysis of these bioactive constituents with preclinical cathepsin L inhibitor (Pub Chem CID: 16725315). The pharmacokinetic properties and toxicity evaluation were calculated by Datawarrior and Osiris Molecular Property explorer software, respectively. Many bioactive constituents from long pepper, ginger, clove, and black pepper have shown significant binding affinity, docking interactions and acceptable pharmacokinetic properties with the human cathepsin L protease. Piperolactam A constituent of long pepper and Kaempferol constituent of clove were found to be more acceptable natural therapeutic compounds among other selected bioactive constituents with the highest binding affinity (Kcal/mol) −9.4 and −9.3, respectively.

Received: 21 August 2023 | Revised: 22 December 2023 | Accepted: 25 December 2023

Conflicts of Interest

P. S. Bisen is an Editorial Board Member for Medinformatics, and was not involved in the editorial review or the decision to publish this article. The authors declare that they have no conflicts of interest to this work.

Data Availability Statement

The data that support the findings of this study are publicly available: Protein Data Bank: https://www.rcsb.org/structure/2XU1; Pub Chem: https://pubchem.ncbi.nlm.nih.gov/compound/16725315