Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
7043891
Reference Type
Journal Article
Title
Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease
Author(s)
Shivanika, C; Kumar, DS; Ragunathan, V; Tiwari, P; Sumitha, A; Devi, BP; ,
Year
2020
Is Peer Reviewed?
Yes
Journal
Journal of Biomolecular Structure & Dynamics
ISSN:
0739-1102
Publisher
TAYLOR & FRANCIS INC
Location
PHILADELPHIA
PMID
32897178
DOI
10.1080/07391102.2020.1815584
Web of Science Id
WOS:000567586000001
Abstract
The study aims to evaluate the potency of two hundred natural antiviral phytocompounds against the active site of the Severe Acquired Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) Main-Protease (M-pro) using AutoDock 4.2.6. The three- dimensional crystal structure of the M-pro(PDB Id: 6LU7) was retrieved from the Protein Data Bank (PDB), the active site was predicted using MetaPocket 2.0. Food and Drug Administration (FDA) approved viral protease inhibitors were used as standards for comparison of results. The compounds theaflavin-3-3'-digallate, rutin, hypericin, robustaflavone, and (-)-solenolide A with respective binding energy of -12.41 (Ki = 794.96 pM); -11.33 (Ki = 4.98 nM); -11.17 (Ki = 6.54 nM); -10.92 (Ki = 9.85 nM); and -10.82 kcal/mol (Ki = 11.88 nM) were ranked top as Coronavirus Disease - 2019 (COVID-19) M(pro)inhibitors. The interacting amino acid residues were visualized using Discovery Studio 3.5 to elucidate the 2-dimensional and 3-dimensional interactions. The study was validated by i) re-docking the N3-peptide inhibitor-M(pro)and superimposing them onto co-crystallized complex and ii) docking decoy ligands to M-pro. The ligands that showed low binding energy were further predicted for and pharmacokinetic properties and Lipinski's rule of 5 and the results are tabulated and discussed. Molecular dynamics simulations were performed for 50 ns for those compounds using the Desmond package, Schrodinger to assess the conformational stability and fluctuations of protein-ligand complexes during the simulation. Thus, the natural compounds could act as a lead for the COVID-19 regimen afterin-vitroandin- vivoclinical trials. Communicated by Ramaswamy H. Sarma
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity