Modulation of the antiviral innate immune response has been proposed as a putative cellular target for the development of novel pan-viral therapeutic strategies. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is especially relevant due to its essential role in the regulation of local and systemic inflammation in response to viral infections, being, therefore, a putative therapeutic target. Here, we review the extraordinary diversity of strategies that viruses have evolved to interfere with JAK-STAT signaling, stressing the relevance of this pathway as a putative antiviral target. Moreover, due to the recent remarkable progress on the development of novel JAK inhibitors (JAKi), the current knowledge on its efficacy against distinct viral infections is also discussed. JAKi have a proven efficacy against a broad spectrum of disorders and exhibit safety profiles comparable to biologics, therefore representing good candidates for drug repurposing strategies, including viral infections.
Keywords: COVID-19; JAK-STAT; antiviral; inflammation; innate immunity; therapeutic strategies; treatment.