HOST-DIRECTED ANTIVIRAL STRATEGIES: REPURPOSING DSRNA VIRUSES FOR BROAD-SPECTRUM PANDEMIC RESPONSE

Abstract

Viral infections are a continuing challenge to the health of the world, because they spread so easily and have a high mutation rate and are becoming resistant to conventional antiviral medications. Antiviral tools are needed to respond quickly to the emergence of new pathogens, as evidenced by the recent epidemics of COVID 19, Ebola and influenza. Traditional antiviral therapies focus on viral proteins and replication mechanism, are, however, often not fully effective due to the rapid evolution of viruses, their limited spectrum of activity and the time needed for a new drug to be developed. These restrictions have led to a resurgence of interest in host directed antiviral therapies as a possible alternate means of therapy. Host directed therapies involve targeting cellular pathways and immune responses in the host that viruses exploit to enter, replicate and survive. This review discusses the mechanisms of host directed antiviral strategies such as the activation of innate immune pathways using Toll like receptor and RIG I like receptor and regulation of cytokine responses, autophagy mediated viral clearance and metabolic reprogramming of infected cells. The antiviral roles of double stranded RNA molecules and their synthetic analogues, including interferon inducers like poly I:C, that promote antiviral immunity against a wide spectrum of viruses is emphasized. The review also underscores the potential of drug repurposing in getting drugs available for viral outbreaks and the diverse families of therapeutic potential of host directed therapies. Furthermore, the challenges of translation, identification of biomarkers and safety and ethics issues with these therapies are discussed. Host directed antiviral therapy is overall an effective approach that can be used in order to increase pandemic preparedness or to create effective broad spectrum antiviral drugs against future emerging viral diseases.