Discovery of cyperenoic acid as a potent and novel entry inhibitor of influenza A virus.
Antiviral Res
; 223: 105822, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38350497
ABSTRACT
Influenza therapeutics with new targets and modes of action are urgently needed due to the frequent emergence of mutants resistant to currently available anti-influenza drugs. Here we report the in vitro and in vivo anti-influenza A virus activities of cyperenoic acid, a natural compound, which was isolated from a Chinese medicine Croton crassifolius Geise. Cyperenoic acid could potently suppress H1N1, H3N2 and H9N2 virus replication with IC50 values ranging from 0.12 to 15.13 µM, and showed a low cytotoxicity against MDCK cells (CC50 = 939.2 ± 60.0 µM), with selectivity index (SI) values ranging from 62 to 7823. Oral or intraperitoneal treatment of cyperenoic acid effectively protected mice against a lethal influenza virus challenge, comparable to the efficacy of Tamiflu. Additionally, cyperenoic acid also significantly reduced lung virus titers and alleviated influenza-induced acute lung injury in infected mice. Mechanism-of-action studies revealed that cyperenoic acid exhibited its anti-influenza activity during the entry stage of viral replication by inhibiting HA-mediated viral fusion. Simulation docking analyses of cyperenoic acid with the HA structures implied that cyperenoic acid binds to the stalk domain of HA in a cavity near the fusion peptide. Collectively, these results demonstrate that cyperenoic acid is a promising lead compound for the anti-influenza drug development and this research provides a useful small-molecule probe for studying the HA-mediated viral entry process.
Key words
Full text:
1
Collection:
01-internacional
Health context:
2_ODS3
Database:
MEDLINE
Main subject:
Sesquiterpenes
/
Influenza, Human
/
Influenza A Virus, H1N1 Subtype
/
Influenza A Virus, H9N2 Subtype
Limits:
Animals
/
Humans
Language:
En
Journal:
Antiviral Res
Year:
2024
Document type:
Article