A synthetic miR-7702: a potential therapeutic approach for SARS-CoV-2 infection

PROJECT SUMMARY Coronavirus disease 2019 (COVID-19) is caused by the newly identified coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus has caused over 775 million infections and more than 7 million deaths worldwide. There is an urgent need to identify host factors that restrict SARS-CoV-2 infection and thus aid in developing novel therapeutics to combat this disease. The long-term goal of this project is to understand the molecular mechanisms of the host factors that regulate SARS-CoV-2 infection and to develop antiviral drugs targeting these host factors. Among host factors, microRNAs (miRNAs) are small noncoding RNAs that control the expression of most genes at the posttranscriptional level. miRNAs have been implicated in diverse biological processes and diseases, including viral infections. Our understanding of the role of host cellular miRNAs in SARS-CoV-2 replication is very limited. We found that miR-7702 was the most potent miRNA in inhibiting SARS-CoV-2 infection by targeting a viral RNA. Our overall objective of the current application is to develop a synthetic miR-7702 as a therapeutic for SARS-CoV-2 infection. We hypothesize that miR-7702 attenuates SARS-CoV-2 infection by targeting a viral RNA. Aim I will delineate the mechanism of action by which miR-7702 exerts its anti-SARS-CoV-2 activity. Aim II will evaluate the in vivo toxicity, biodistribution and therapeutic efficacy of a synthetic miR-7702 mimic against SARS-CoV-2 infection in a preclinic mouse model. We expect to establish a previously unrecognized role for host miR-7702 in the repression of SARS-CoV-2 replication and provide preclinical data for miR-7702 as a therapeutic for SARS- CoV-2 infection.