Figure 4.

Inhibition of the exoribonuclease activity of SARS-CoV-2 nsp14 by ebselen and disulfiram. (A) SARS-CoV-2 nsp14 degraded the FAM-labeled 37-nucleotide ssRNA (5′-FAM-C₇U₃₀-3′) into small fragments as revealed in the TBE gel (right panel). Increased concentrations of ebselen (0–100 μM) gradually inhibited nsp14 exoribonuclease activity with an estimated IC₅₀ of 3.18 μM (left panel). (B) Disulfiram inhibited the exoribonuclease activity of nsp14 with an estimated IC₅₀ of 2.70 μM. In the two gels, the relative nuclease activity (%) was estimated based on the band intensity of the cleaved products, normalized to that in the first lane (no drug, 100% activity) and that in the second to last lane corresponding to 0% activity with 100 μM ebselen or 200 μM disulfiram. Error bars shown in the two left panels represent the standard errors from three replicates of the experiment.