Identification of tyrphostin AG879 and A9 inhibiting replication of chikungunya virus by screening of a kinase inhibitor library.

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. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Yanhua He, Zhendong Pan, Yan Liu, Liangliang Jiang, Haoran Peng, Ping Zhao, Zhongtian Qi, Yangang Liu, Hailin Tang. Identification of tyrphostin AG879 and A9 inhibiting replication of chikungunya virus by screening of a kinase inhibitor library. Virology. 2023 Nov;588:109900

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PMID: 37832343

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