Azacytidine targeting SARS-CoV-2 viral RNA as a potential treatment for COVID-19

The COVID-19 pandemic is a global health disaster. Moreover, emerging mutated virus strains present an even greater challenge for existing vaccines and medications. One possible solution is to design drugs based on the properties of virus epigenome, which are more common among coronaviruses. Here, we reported an FDA-approved drug for myelodysplastic syndrome, azacytidine (5Aza), limited virus infection and protected mice against SARS-CoV-2. We demonstrated that this antiviral effect is related to 5Aza incorporation into viral RNA, which disrupt m5C RNA methylation modification profile. This work suggests that targeting viral epigenomes is a viable therapeutic strategy, potentially opening new pathways for treating COVID-19.