Abstract 2497 Viral RNA Cap Blockers: Targeting Coronaviral RNA Methyltransferases

Coronaviruses (CoVs) have been a serious threat to global human health due to the emergence of pathogenic CoVs able to cause disease in humans, such as the now endemic SARS-CoV-2. As part of the response to COVID-19 pandemic and in preparation for the potential emergence of novel CoVs in the future, we focused on finding inhibitors to target the SARS-CoV-2 methyltransferases nsp14-10 and nsp16-nsp10 complexes, using structure-based drug design. These two protein complexes perform two out of three steps of viral RNA capping, forming the Cap-0-RNA and Cap-1-RNA respectively.