Fig. 2: Characterization of novel NSP14/10 inhibitors.

a Chemical structures of the three compounds (#79, #96 and #102) that performed the best in the viral infection assays. Compound #38, which does not inhibit NSP14, was included in downstream assays as a negative control. b Dose-response curves of NSP14/10 activity in the presence of compounds #38 (negative control), #79, #96 and #102. Average IC₅₀ values were calculated from three independent measurements using technical duplicates. Error bars represent SD. c A gel-based assay was used to verify inhibitory potential of compounds #79, #96, #102, and #38. Inhibition of the NSP14/10 exonuclease activity results in the reduction of the full-length dsRNA oligo and increase in faster migrating bands. Compounds were used at the indicated concentrations. d Differential scanning fluorimetry performed in the presence or absence of the indicated compounds at 50 μM concentrations. Graph shows calculated mean melting temperatures of the NSP14/10 complex in the presence of the indicated compounds. Error bars represent SD. e Docking poses of compounds, predicted to stack either against the last nucleobase (#79, #96) or under the RNA (#102) while simultaneously engaging the Mg²⁺ ion(s) at the catalytic site (red dots).