Exploring non-traditional targets for antiviral therapy – novel inhibitors of SARS-CoV-2 methyltransferases

Exploring non-traditional targets for antiviral therapy – novel inhibitors of SARS-CoV-2 methyltransferases Radim Nencka, PhD Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, 160 00 Praha 6, Czech Republic SARS-CoV-2 has caused a global pandemic that affected lives of billions of people and changed our view on our preparedness for global health treads as well as their effects on economic situation worldwide. This situation uncovered the lack of effective therapeutic approaches against infectious pathogens and an urgent need for novel approaches to effectively fight the diseases that they cause. In collaboration with our partners from both academia and industry, we have been trying to explore several underestimated molecular targets for SARS-CoV-2. In particular, we have been interested in virus methyltransferases (MTases) that are responsible for methylation of a cap of viral RNA (vRNA). The methylated cap is essential for protection of vRNA against innate immunity and start of effective translation. SARS-CoV-2 encodes two MTases – which are nsp14 and nsp16, which uses a nsp10 protein as cofactor for efficient methylation. My lecture will focus on our progress in design of novel inhibitors of both SARS-CoV-2 MTases.