Identification of tyrphostin AG879 and A9 inhibiting replication of chikungunya virus by screening of a kinase inhibitor library.
Virology
; 588: 109900, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37832343
ABSTRACT
Chikungunya virus (CHIKV) is a globally public health threat. There are currently no medications available to treat CHIKV infection. High-throughput screening of 419 kinase inhibitors was performed based on the cytopathic effect method, and six kinase inhibitors with reduced cytopathic effects, including tyrphostin AG879 (AG879), tyrphostin 9 (A9), sorafenib, sorafenib tosylate, regorafenib, and TAK-632, were identified. The anti-CHIKV activities of two receptor tyrosine kinase inhibitors, AG879 and A9, that have not been previously reported, were selected for further evaluation. The results indicated that 50% cytotoxic concentration (CC50) of AG879 and A9 in Vero cells were greater than 30 µM and 6.50 µM, respectively and 50% effective concentration (EC50) were 0.84 µM and 0.36 µM, respectively. The time-of-addition and time-of-removal assays illustrated that both AG879 and A9 function in the middle stage of CHIKV life cycle. Further, AG879 and A9 do not affect viral attachment; however, they inhibit viral RNA replication, and exhibit antiviral activity against CHIKV Eastern/Central/South African and Asian strains, Ross River virus and Sindbis virus in vitro.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus Chikungunya
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Febre de Chikungunya
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Virology
Ano de publicação:
2023
Tipo de documento:
Article