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Here, we have developed a green\u2010emitting fluorogenic probe, which exhibits a large fluorescence response at 520\u2005nm (&gt;560\u2010fold) when treated with 100\u2005\u03bcM H<jats:sub>2<\/jats:sub>S for 1\u2005h. It is highly selective for H<jats:sub>2<\/jats:sub>S over biothiols (&gt;400\u2010fold <jats:italic>F<\/jats:italic>\/<jats:italic>F<\/jats:italic><jats:sub>0<\/jats:sub>) and has a detection limit of 12.9\u2005nM. We demonstrate the application of the probe for endogenous H<jats:sub>2<\/jats:sub>S detection <jats:italic>in\u2005vivo<\/jats:italic> for the understanding of its roles in antiviral host defense. Such virus\u2010induced H<jats:sub>2<\/jats:sub>S inhibits viral replication by reducing gene expression of RNA\u2010dependent RNA polymerase (RdRp) and coat protein (CP). Additionally, a H<jats:sub>2<\/jats:sub>S donor GYY4137 showed significantly antiviral activity as ribavirin, a broad\u2010spectrum drug against RNA viruses. Furtherly, we propose a possible molecular mechanism for the TMV\u2010induced H<jats:sub>2<\/jats:sub>S biogenesis. This work provides a proof\u2010of\u2010principle in support of further studies identifying endogenous H<jats:sub>2<\/jats:sub>S and its donors as potential antivirals toward RNA viruses.<\/jats:p>","DOI":"10.1002\/cbic.202100138","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T22:19:53Z","timestamp":1619129993000},"page":"2292-2299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A H<sub>2<\/sub>S\u2010Specific Ultrasensitive Fluorogenic Probe Reveals TMV\u2010Induced H<sub>2<\/sub>S Production to Limit Virus Replication"],"prefix":"10.1002","volume":"22","author":[{"given":"Zhili","family":"Pang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, National Engineering Research Center of Pesticide (Tianjin) College of Chemistry Nankai University  Tianjin 300071 P. R. 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