Abstract
We have recently shown that endogenous hydrogen sulfide (H₂S), an important cellular gaseous mediator, exerts an antiviral and anti-inflammatory activity in vitro and in vivo, and that exogenous H₂S delivered via the synthetic H₂S-releasing compound GYY4137 also has similar properties. In this study, we sought to extend our findings to a novel class of H₂S donors, thiol-activated gem-dithiol-based (TAGDDs). In an in vitro model of human respiratory syncytial virus (RSV) infection, TAGDD-1 treatment significantly reduced viral replication, even when added up to six hours after infection. Using a mouse model of RSV infection, intranasal delivery of TAGDD-1 to infected mice significantly reduced viral replication and lung inflammation, markedly improving clinical disease parameters and pulmonary dysfunction, compared to vehicle treated controls. Overall our results indicate that this novel synthetic class of H₂S-releasing compounds exerts antiviral and anti-inflammatory activity in the context of RSV infection and represents a potential novel pharmacological approach to ameliorate viral-induced lung disease.