Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 M through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities fo...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2024-06, Vol.25 (12), p.6715
Main Authors: Bastos, Ruan S, de Aguiar, Christiane P O, Cruz, Jorddy N, Ramos, Ryan S, Kimani, Njogu M, de Souza, João S N, Chaves, Mariana H, de Freitas, Humberto F, Pita, Samuel S R, Santos, Cleydson B R Dos
Format: Article
Language:English
Subjects:
Amino acids
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
binding affinity
Biological activity
Brain research
Coronavirus 3C Proteases - antagonists & inhibitors
Coronavirus 3C Proteases - chemistry
Coronavirus 3C Proteases - metabolism
Coronaviruses
COVID-19
COVID-19 - virology
COVID-19 Drug Treatment
Disease transmission
drug development
Drug dosages
Genomes
Health aspects
Humans
Hydrogen Bonding
Ligands
Metabolism
molecular docking
Molecular Docking Simulation
molecular dynamics
Molecular Dynamics Simulation
Pandemics
Peptides
Permeability
Pharmacokinetics
Protease inhibitors
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Protein Binding
Proteins
RNA polymerase
SARS-CoV-2
SARS-CoV-2 - drug effects
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Toxicity
Zoonoses
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 M through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for M , ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and M , with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with M catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25126715