ABSTRACT
Aim To investigate the inhibitory effect of copper gluconate and disulfiran on the PLpro of SARS-CoV-2 and to explore the effect of combination of them on PLpro.Methods SARS-CoV-2 PLpro was purified by recombinant expression technology of he effects of copper gluconate and disulfiram on PLpro activity were studied by enzyme kinetic method.Results Copper gluconate and disulfiram had high inhibitory activity on SARS-CoV-2 PLpro,Ubiquitin-7-Amino-4-methylcoumarin(Ub-AMC)was used as the fluorescent substrate.The IC50 of copper gluconate was 33.02 nmol·L-1,showing competitive inhibition,and the IC50 of disulfiram was 480.4 nmol·L-1,showing non competitive inhibition,and the combination of the two inhibitors showed the advantage of synergistic inhibition.Conclusions Copper gluconate and disulfiram have a high inhibitory effect on SARS-CoV-2 PLpro protein,and the combination shows the advantage of synergistic inhibition.