Abstract
SARS-CoV-2, the viral particle, is responsible for triggering the 2019 Coronavirus disease outbreak (COVID-19). To tackle this situation, a number of strategies are being devised to either create an antidote, a vaccine, or agents capable of preventing its infection. To enable research on these strategies, numerous target proteins are identified where Spike (S) protein is presumed to be of immense potential. S-protein interacts with human angiotensin-converting-enzyme-2 (ACE2) for cell entry. The key region of S-protein that interacts with ACE2 is a portion of it designated as a receptor-binding domain (RBD), following whereby the viral membrane fuses with the alveolar membrane to enter the human cell. The proposition is to recognize molecules from the bundle of phytochemicals of medicinal plants known to possess antiviral potentials as a lead that could interact and mask RBD, rendering them unavailable to form ACE2 interactions. Such a molecule is called the ‘S-protein blocker’. A total of 110 phytochemicals from Withania somnifera, Asparagus racemosus, Zinziber officinalis, Allium sativum, Curcuma longa and Adhatoda vasica were used in the study, of which Racemoside A, Ashwagandhanolide, Withanoside VI, Withanoside IV and Racemoside C were identified as top five hits using molecular docking. Further, essential Pharmacophore features and their ADMET profiles of these compounds were studied following to which the best three hits were analyzed for their interaction with RBD using Molecular Dynamics (MD) simulation. Binding free energy calculations were performed using MM/GBSA, proving these phytochemicals can serve as S-protein blocker.
Keywords: Antiviral phytochemicals; Molecular dynamics (MD) simulation; S-Protein blocker; SARS-CoV-2 novel coronavirus.
【저자키워드】 molecular dynamics (MD) simulation, Antiviral phytochemicals, S-Protein blocker, SARS-CoV-2 novel coronavirus., 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, ACE2, Vaccine, Antiviral, spike, Dynamics, Infection, molecular docking, molecular dynamics, Free energy calculation, pharmacophore, free energy, Novel coronavirus, Protein, Receptor-binding domain, outbreak, RBD, Research, membrane, plant, molecules, disease outbreak, disease, interactions, Interaction, Antidote, S-protein, angiotensin, lead, Bundle, profile, enzyme, viral membrane, domain, cell entry, portion, these compounds, target protein, viral particle, human cell, alveolar, triggering, FIVE, feature, proposition, responsible, analyzed, performed, were used, recognize, interact, these compound, Allium, Asparagus, Curcuma, racemosus, 【제목키워드】 SARS-CoV-2, ACE2, Antiviral, molecular, Interaction,