The authors identify that H2S has a protective role in paramyxovirus infection by modulating inflammatory responses and viral replication. In this study, they tested the antiviral and anti-inflammatory activity of an H2S donor on enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families, for which there is no FDA-approved vaccine or therapeutic available, with the exception of influenza. They found that this approach significantly reduced replication of all tested viruses. In a model of influenza infection, this treatment was associated with decreased expression of viral proteins and mRNA, suggesting inhibition of an early step of replication. The antiviral activity coincided with the decrease of viral-induced pro-inflammatory mediators and viral-induced nuclear translocation of transcription factors from Nuclear Factor (NF)-kB and Interferon Regulatory Factor families. In conclusion, increasing cellular H2S is associated with significant antiviral activity against a broad range of emerging enveloped RNA viruses, and should be further explored as potential therapeutic approach in relevant pre-clinical models of viral infections.
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