Structure of the SARS-CoV-2 RNA-dependent RNA polymerase in the presence of favipiravir-RTP

Favipiravir is a purine nucleic acid analogue that acts as a chain terminator of RNA synthesis by the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). In this report, the structure of SARS-CoV-2 RdRp comprising of nsp7, nsp8 and nsp12 in complex with template:primer double-stranded RNA (dsRNA) associated with favipiravir-ribonucleoside triphosphate (favipiravir-RTP) was determined by cryo-EM. SARS-CoV-2 proteins were purified by using baculoviral and bacterial expression systems, and in vitro RNA synthesis assay was carried out by using an approximately 30 nucleotides dsRNA as a template:primer, which was further subjected to Cryo-EM observation. Cryo-EM revealed the association of favipiravir-RTP with catalytic site of viral RdRp at a high resolution.