G-quadruplex ligands inhibit chikungunya virus replication

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus affecting human health globally. G-quadruplex secondary structures attract great attention as potential targets for antiviral strategy. In this study, we show that the CHIKV genome possesses several conserved potential G-quadruplex sequences. G-quadruplex ligands BRACO-19 and TMPyP4 could stabilize the CHIKV G-quadruplex and inhibit the transcription of constructs containing CHIKV G-quadruplex sequences. Importantly, BRACO-19 and TMPyP4 suppress CHIKV replication. Our study not only reinforces the presence of viral G-quadruplex sequences but also suggests that targeting G-quadruplex structure could represent a novel strategy to inhibit CHIKV. Highlights CHIKV possesses conserved G-quadruplexes G-quadruplex ligands stabilize CHIKV G-quadruplexes with high affinities G-quadruplex structures reduce the transcription of the GFP reporter gene containing CHIKV G-quadruplex G-quadruplex ligands BRACO-19 and TMPyP4 inhibit CHIKV replication