Korupensamine A, but not its atropisomer, korupensamine B, inhibits SARS-CoV-2 in vitro by targeting its main protease (M
Alkaloids
M(pro)
Naphthylisoquinolines
Natural products
SARS-CoV-2
Steered molecular dynamics
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 May 2023
05 May 2023
Historique:
received:
05
12
2022
revised:
07
02
2023
accepted:
20
02
2023
medline:
4
4
2023
pubmed:
10
3
2023
entrez:
9
3
2023
Statut:
ppublish
Résumé
By combining docking and molecular dynamics simulations, we explored a library of 65 mostly axially chiral naphthylisoquinoline alkaloids and their analogues, with most different molecular architectures and structural analogues, for their activity against SARS-CoV-2. Although natural biaryls are often regarded without consideration of their axial chirality, they can bind to protein targets in an atroposelective manner. By combining docking results with steered molecular dynamics simulations, we identified one alkaloid, korupensamine A, that atropisomer-specifically inhibited the main protease (M
Identifiants
pubmed: 36893625
pii: S0223-5234(23)00192-7
doi: 10.1016/j.ejmech.2023.115226
pmc: PMC9972725
pii:
doi:
Substances chimiques
korupensamine A
0
Antiviral Agents
0
Protease Inhibitors
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115226Informations de copyright
Copyright © 2023 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.