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© 2021 Wiley–VCH GmbHUnderstanding the role of H2S in host defense mechanisms against RNA viruses may provide opportunities for the development of antivirals to combat viral infections. Here, we have developed a green–emitting fluorogenic probe, which exhibits a large fluorescence response at 520 nm (>560–fold) when treated with 100 μM H2S for 1 h. It is highly selective for H2S over biothiols (>400–fold F/F0) and has a detection limit of 12.9 nM. We demonstrate the application of the probe for endogenous H2S detection in vivo for the understanding of its roles in antiviral host defense. Such virus–induced H2S inhibits viral replication by reducing gene expression of RNA–dependent RNA polymerase (RdRp) and coat protein (CP). Additionally, a H2S donor GYY4137 showed significantly antiviral activity as ribavirin, a broad–spectrum drug against RNA viruses. Furtherly, we propose a possible molecular mechanism for the TMV–induced H2S biogenesis. This work provides a proof–of–principle in support of further studies identifying endogenous H2S and its donors as potential antivirals toward RNA viruses.
