Abstract
The outbreak of COVID-19 disease caused by SARS-CoV-2, along with the lack of targeted medicaments, forced the scientific world to search for new antiviral formulations. In the current emergent situation, drug repurposing of well-known traditional and/or approved drugs could be the most effective strategy. Herein, through computational approaches, we aimed to screen 14 natural compounds from limonoids and terpenoids class for their ability to inhibit the key therapeutic target proteins of SARS-CoV-2. Among these, some limonoids, namely deacetylnomilin, ichangin and nomilin, and the terpenoid β-amyrin provided good interaction energies with SARS-CoV-2 3CL hydrolase (Mpro) in molecular dynamic simulation. Interestingly, deacetylnomilin and ichangin showed direct interaction with the catalytic dyad of the enzyme so supporting their potential role in preventing SARS-CoV-2 replication and growth. On the contrary, despite the good affinity with the spike protein RBD site, all the selected phytochemicals lose contact with the amino acid residues over the course of 120ns-long molecular dynamics simulations therefore suggesting they scarcely can interfere in SARS-CoV-2 binding to the ACE2 receptor. The in silico analyses of docking score and binding energies, along with predicted pharmacokinetic profiles, indicate that these triterpenoids might have potential as inhibitors of SARS-CoV-2 Mpro, recommending further in vitro and in vivo investigations for a complete understanding and confirmation of their inhibitory potential.
Keywords: Docking; Limonoids; Molecular dynamics; Protease; SARS-CoV-2; Spike protein; Terpenoids.
【저자키워드】 SARS-CoV-2, docking, molecular dynamics, protease, Spike protein, terpenoids, Limonoids, 【초록키워드】 Drug repurposing, Antiviral, spike, ACE2 receptor, docking, molecular dynamics, protease, in vitro, in silico, inhibitors, Spike protein, Molecular dynamics simulation, Computational approaches, COVID-19 disease, MPro, SARS-CoV-2 Mpro, Protein, outbreak, RBD, molecular, in vivo, SARS-CoV-2 replication, binding, Amino acid, pharmacokinetic, Interaction, Analysis, Contact, therapeutic target, contact with, approved drug, confirmation, inhibitors of SARS-CoV-2, enzyme, growth, Compound, hydrolase, profiles, contrary, amino acid residues, catalytic dyad, docking score, inhibitory, amino acid residue, Complete, effective, 3CL hydrolase, Course, selected, predicted, lack, caused, inhibit, provided, the spike protein, interfere, 【제목키워드】 molecular docking, in silico, therapeutic, selected,