Discovery of cyperenoic acid as a potent and novel entry inhibitor of influenza A virus.
Antiviral Res
; 223: 105822, 2024 03.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sesquiterpenos
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Gripe Humana
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Subtipo H1N1 del Virus de la Influenza A
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Subtipo H9N2 del Virus de la Influenza A
Límite:
Animals
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Humans
Idioma:
En
Revista:
Antiviral Res
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos