Unravelling the therapeutic potential of marine drugs as SARS-CoV-2 inhibitors: An insight from essential dynamics and free energy landscape

Abstract

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic. The virus that causes the disease, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), predominantly infects the respiratory tract, which may lead to pneumonia and death in severe cases. Many marine compounds have been found to have immense medicinal value and have gained approval from the Food and Drug Administration (FDA), and some are being tested in clinical trials. In the current investigation, we redirected a number of marine compounds toward SARS-CoV-2 by targeting the main protease (M pro , PDB ID: 6Y2F), subjecting them to several advanced computational techniques using co-crystallised ligand as the reference compound. The results of the binding affinity studies showed that two compounds, eribulin mesylate (eri) and soblidotin (sob), displayed higher docking scores than did the reference compound. When these compounds were assessed using molecular dynamics simulation, it was evident that they demonstrated stable binding at the binding pocket of the target protein. The systems demonstrated stable root mean square deviation and radius of gyration values, while occupying the binding pocket during the simulation run. Furthermore, the essential dynamics and free energy landscape exploration revealed that the protein had navigated through a minimal energy basin and demonstrated favourable conformation while binding to the proposed inhibitors. Collectively, our findings suggest that two marine compounds, namely eri and sob, show potential as SARS-CoV-2 main protease inhibitors.

An understanding of coronavirus and exploring the molecular dynamics simulations to find promising candidates against the Mpro of nCoV to combat the COVID-19: A systematic review

“…The average number of H-bonds with eri and sob was 1.9 and 2.1. This indicates that the ligand is in the required capsule and interacts with the target protein throughout the simulation [80] . MD simulations of Lucenin-2, Saponarin and isoschaftoside with Mpro of nCoV (6LU7) was done using AMBER.…”

“… [79] Mpro (6Y2F) Eribulin mesylate (eri) Soblidotin (sob) Binding energy (kcal/mol) -96.60 -76.32 GROMACS Hydrogen bond and π-alkyl interactions with key residues based on MD simulations. [80] Mpro (6LU7) Lucenin-2 Saponarin Isoschaftoside Binding Energy (kcal/mol) -10.7 -10.6 -10.5 AMBER MM-PB(GB)SA Compounds from Passiflora sp. showed potential ability based on molecular docking and MD simulations [81] Mpro (6Y7M).…”

Characterization of Plant-Derived Natural Inhibitors of Dipeptidyl Peptidase-4 as Potential Antidiabetic Agents: A Computational Study

“…A free energy landscape (FEL) depicts the potential energy of a system about its pertinent variables [ 88 ], offering insights into the energy obstacles and favorable states a molecule explores during transitions between various conformations or states [ 89 ]. Based on the simulation trajectories, RMSD and RG values were computed for every frame, forming a density matrix that characterized a distinct area within the conformational space, and subsequently, the Gibbs free energy surface was determined by this density matrix and principles of statistical mechanics [ 90 ].…”

Natural Bioactive Molecules: An Alternative Approach to the Treatment and Control of COVID-19

“…In silico analyses have recently contributed in the identification of potential lead compounds for therapeutic development against the COVID-19 pandemic. In a molecular dynamic research, Khan et al [ 181 ] reported four effective SARS-CoV-2 M pro inhibitors from marine sources (fostularin 3,1-hexadecoxypropane-1, 2-diol, palmitoleic acid, 15 alphamethoxypuupehenol, and puupehedione) that can be used to disrupt the viral life cycle in the host.…”