Exploring the structural and molecular interaction landscape of nirmatrelvir and Mpro complex: The study might assist in designing more potent antivirals targeting SARS-CoV-2 and other viruses.
Mpro-nirmatrelvir complex
Nirmatrelvir
SARS-CoV-2
Structural and molecular interaction landscape
Journal
Journal of infection and public health
ISSN: 1876-035X
Titre abrégé: J Infect Public Health
Pays: England
ID NLM: 101487384
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
10
06
2023
revised:
25
09
2023
accepted:
28
09
2023
medline:
27
11
2023
pubmed:
27
10
2023
entrez:
26
10
2023
Statut:
ppublish
Résumé
Several therapeutics have been developed and approved against SARS-CoV-2 occasionally; nirmatrelvir is one of them. The drug target of nirmatrelvir is Mpro, and therefore, it is necessary to comprehend the structural and molecular interaction of the Mpro-nirmatrelvir complex. Integrative bioinformatics, system biology, and statistical models were used to analyze the macromolecular complex. Using two macromolecular complexes, the study illustrated the interactive residues, H-bonds, and interactive interfaces. It informed of six and nine H-bond formations for the first and second complex, respectively. The maximum bond length was observed as 3.33 Å. The ligand binding pocket's surface area and volume were noted as 303.485 Å Our study reveals the structural and molecular interaction landscape of Mpro-nirmatrelvir complex. The study will guide researchers in designing more broad-spectrum antiviral molecules mimicking nirmatrelvir, which assist in fighting against SARS-CoV-2 and other infectious viruses. It will also help to prepare for future epidemics or pandemics.
Sections du résumé
BACKGROUND
BACKGROUND
Several therapeutics have been developed and approved against SARS-CoV-2 occasionally; nirmatrelvir is one of them. The drug target of nirmatrelvir is Mpro, and therefore, it is necessary to comprehend the structural and molecular interaction of the Mpro-nirmatrelvir complex.
METHODS
METHODS
Integrative bioinformatics, system biology, and statistical models were used to analyze the macromolecular complex.
RESULTS
RESULTS
Using two macromolecular complexes, the study illustrated the interactive residues, H-bonds, and interactive interfaces. It informed of six and nine H-bond formations for the first and second complex, respectively. The maximum bond length was observed as 3.33 Å. The ligand binding pocket's surface area and volume were noted as 303.485 Å
CONCLUSIONS
CONCLUSIONS
Our study reveals the structural and molecular interaction landscape of Mpro-nirmatrelvir complex. The study will guide researchers in designing more broad-spectrum antiviral molecules mimicking nirmatrelvir, which assist in fighting against SARS-CoV-2 and other infectious viruses. It will also help to prepare for future epidemics or pandemics.
Identifiants
pubmed: 37883855
pii: S1876-0341(23)00327-1
doi: 10.1016/j.jiph.2023.09.020
pii:
doi:
Substances chimiques
Antiviral Agents
0
Lactams
0
Nitriles
0
Coronavirus 3C Proteases
EC 3.4.22.28
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1961-1970Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing interests.