<p>Corona viruses were first
identified in 1931 and SARS-CoV-2 is the most recent. COVID-19 is a pandemic
that put most of the world on lockdown and the search for therapeutic drugs is
still on-going. Therefore, this study uses <i>in silico</i> screening to
identify natural bioactive compounds from fruits, herbaceous plants and marine
invertebrates that are able to inhibit protease activity in SARS-CoV-2(PDB:
6LU7). We have used various screening strategies such as drug likeliness,
antiviral activity value prediction, molecular docking, ADME (absorption,
distribution, metabolism, and excretion), molecular dynamics (MD) simulation
and MM/GBSA (molecular mechanics/generalized born and surface area continuum
solvation). 17 compounds were shortlisted using Lipinski’s rule. 5 compounds
revealed significantly good predicted antiviral activity values and out of them
only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy values of -9.22 and -8.00
kcal/mol within the binding pocket,
catalytic residues (HIS 41 and CYS 145) of M<sup>pro</sup>.
These two compounds were further analyzed for their ADME properties. The ADME evaluation of these 2 compounds
suggested that they could be effective as therapeutic agents for developing drugs for clinical trials. MD simulations showed that
protein-ligand complexes of Macrolactin A and Stachyflin were stable for 100
nano seconds. The MM/GBSA calculations of M<sup>pro</sup> – Macrolactin A
complex indicated higher binding free energy (-42.58 ± 6.35 kcal/mol) with M<sup>pro </sup>protein
target receptor (6LU7). DCCM and PCA analysis on the residual movement in the
MD trajectories confirmed the good stability on Macrolactin A bound state of
6LU7. This signify the stable conformation of 6LU7 with high binding energy
with Macrolactin A. Thus, this study showed that Macrolactin A could be an
effective therapeutical agent for SARS-CoV-2protease (6LU7) inhibition.
Additional <i>in vitro </i>and<i> in vivo </i>validations are needed to
determine efficacy and dose of Macrolactin A in biological systems.</p>
Macrolactin A as a Novel Inhibitory Agent for SARS-CoV-2 Mpro: Bioinformatics Approach
