Host microRNA interactions with the SARS-CoV-2 viral genome 3'-untranslated region.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now plagued the world for over three years. In this time, scientific advancements have allowed for the development of mRNA vaccines and targeted antiviral drugs. However, many mechanisms of the viral life cycle, as well as the interactions at the host-virus interface, remain unknown. The host immune response is of particular interest in combating SARS-CoV-2 infection, with observed dysregulation in both severe and mild cases of infection. To uncover the link between SARS-CoV-2 infection and observed immune dysregulation, we investigated host microRNAs associated with the immune response, particularly miR-760-3p, miR-34a-5p, and miR-34b-5p and emphasize them as targets of binding by the viral genome 3'-UTR. We utilized biophysical methods to characterize the interactions between these miRs and the SARS-CoV-2 viral genome 3'-UTR. Lastly, we introduce 2'-fluoro-D-arabinonucleic acid analogs of these microRNAs as disruptors of the binding interactions, with intent of therapeutic intervention.