A H2 S-Specific Ultrasensitive Fluorogenic Probe Reveals TMV-Induced H2 S Production to Limit Virus Replication
Zhili Pang1, Haishun Ye2, Dejun Ma1
1State 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. China.
Abstract:
Understanding the role of H2 S 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 H2 S for 1 h. It is highly selective for H2 S over biothiols (>400-fold F/F0 ) and has a detection limit of 12.9 nM. We demonstrate the application of the probe for endogenous H2 S detection in vivo for the understanding of its roles in antiviral host defense. Such virus-induced H2 S inhibits viral replication by reducing gene expression of RNA-dependent RNA polymerase (RdRp) and coat protein (CP). Additionally, a H2 S 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 H2 S biogenesis. This work provides a proof-of-principle in support of further studies identifying endogenous H2 S and its donors as potential antivirals toward RNA viruses.
