id author title date pages extension mime words sentences flesch summary cache txt cord-351837-vasuu70k Shannon, Ashleigh Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis 2020-09-17 .txt text/plain 6507 349 50 title: Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. This enzyme readily incorporates T-705-ribose-5′-phosphate into viral RNA in vitro, and cell culture based infectious virus studies show an increase in mutations in the presence of Favipiravir. To determine the efficacy and MoA of T-705 against SARS-CoV we first characterised nsp12 primerdependent activity using traditional annealed primer-template (PT) and self-priming hairpin (HP) RNAs that may confer additional stability on the elongation complex ( Supplementary Fig. 1c) . These data reveal that the SARS-CoV nsp12 is the fastest viral RdRp known, with rates significantly faster than the 5-20 s −1 observed for picornaviral polymerases at room temperature [33] [34] [35] and 4-18 s −1 for hepatitis C and dengue virus polymerases at 30 and 37°C 36, 37 . ./cache/cord-351837-vasuu70k.txt ./txt/cord-351837-vasuu70k.txt