Fig. 2: Excision of bemnifosbuvir and sofosbuvir by SARS-CoV-2 ExoN.
From: Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals
a Fluorescence polarization analysis of the binding between SARS-CoV-2 ExoN and T20P14-U, T20P14-S, T20P14-G, or T20P14-B. 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. b Digestion of T20P14-U, T20P14-S, T20P14-G, or T20P14-B by SARS-CoV-2 ExoN. The exonucleolytic digestion reactions were stopped at the indicated time points. The RNA products were resolved by denaturing PAGE and visualized by FAM imaging. A representative result from three biological replicates is shown. c Percentages of substrate RNAs remaining shown in (b) were quantified using Bio-Rad Image Lab from three independent experiments and are shown as mean ± SEM. The results were plotted in GraphPad Prism using the One-phase decay model. Decay rates (k) of T20P14-U, T20P14-S, T20P14-G, and T20P14-B are indicated. Statistical analyses were performed using the two-sided extra sum-of-squares F test. P values for the comparisons of decay rate constants are indicated. SARS-CoV-2 ExoN rescues d bemnifosbuvir- or e sofosbuvir-inhibited RNA synthesis. RNA extension reactions were performed in the absence or presence of WT ExoN or ExoN E191A mutant and stopped at the indicated time points. The RNA products were resolved by denaturing PAGE and visualized by FAM imaging. A representative result from three biological replicates is shown. Source data are provided as a Source Data file.
