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A H<sub>2</sub>S‐Specific Ultrasensitive Fluorogenic Probe Reveals TMV‐Induced H<sub>2</sub>S Production to Limit Virus Replication

Zhili Pang, Haishun Ye, Dejun Ma, Xiaoqiang Tu, Long Yi, Zhen Xi

2021ChemBioChem12 citationsDOI

Abstract

Abstract Understanding the role of H 2 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 (&gt;560‐fold) when treated with 100 μM H 2 S for 1 h. It is highly selective for H 2 S over biothiols (&gt;400‐fold F / F 0 ) and has a detection limit of 12.9 nM. We demonstrate the application of the probe for endogenous H 2 S detection in vivo for the understanding of its roles in antiviral host defense. Such virus‐induced H 2 S inhibits viral replication by reducing gene expression of RNA‐dependent RNA polymerase (RdRp) and coat protein (CP). Additionally, a H 2 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 H 2 S biogenesis. This work provides a proof‐of‐principle in support of further studies identifying endogenous H 2 S and its donors as potential antivirals toward RNA viruses.

Topics & Concepts

RNAVirologyViral replicationVirusRNA-dependent RNA polymeraseBiogenesisBiologyEndogenyTobacco mosaic virusDetection limitChemistryRNA virusMolecular biologyGeneBiochemistryChromatographySulfur Compounds in BiologyFibroblast Growth Factor ResearchSulfur-Based Synthesis Techniques