Figure 4. IC₅₀ values for inhibition of RdRp activity of NS5B by Nuc (3′-d′CTP) and NNIs.

Numbers represent mean and standard deviation of IC₅₀ values determined for each inhibitor against the set of NS5B constructs. Heatmap is colored according to IC₅₀ fold shift relative to Δ21 to show changes in inhibition profile for given NNI across NS5B mutant constructs. Thumb site II inhibitors begin to show significant loss of inhibitory potency as interactions between β-loop and C-terminal residues are disrupted by mutations in the interface (Δ21-AAA, truncations past Δ39 and Δ21-Δ39 mutations). Palm site I inhibitor is affected as well, which is explained by disruption of the inhibitor's interaction with the β-loop and C-terminal residues. Inhibition by thumb site I remains for the most part unaffected by NS5B mutations whereas inhibition by palm site II NNI is reduced due to decrease in binding to NS5B with truncated β-loop and/or C-terminal.