Fig. 1: Incorporation of bemnifosbuvir and sofosbuvir by SARS-CoV-2 RdRp.
From: Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals
Chemical structure of a bemnifosbuvir 5′-triphosphate (BTP) and b sofosbuvir 5′-triphosphate (STP) in comparison with their cognate natural NTPs. The characteristic 2′-fluoro-2′-C-methyl groups of bemnifosbuvir and sofosbuvir are highlighted by dashed magenta boxes. c Incorporation of BMP and SMP, respectively, into T20P14 RNAs by SARS-CoV-2 RdRp. Sequence and numbering of the substrate T20P14 RNAs used for bemnifosbuvir or sofosbuvir incorporation are indicated. T-RNA and P-RNA regions are colored in red and blue, respectively, and connected by a UUCG tetraloop. d Fluorescence polarization analysis of the binding between SARS-CoV-2 RdRp and T20P14-U, T20P14-S, T20P14-G, or T20P14-B. Dissociation constant (KD) values are indicated. Each data point represents the mean of nine biological replicates ± SEM. Dissociation constant (KD) values are indicated. Statistical analyses were performed using the two-sided extra sum-of-squares F test. P values for the comparisons of KD values are indicated. Source data are provided as a Source Data file.
