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.
ABSTRACT
Objective: To observe the clinical effect of acupoint sticking therapy with Mian Tan Gao (facial paralysis paste) plus electroacupuncture (EA) for treating peripheral facial paralysis and its influence on patients' facial nerve functions, facial disability index and clinical symptoms and signs. Methods: A total of 96 peripheral facial paralysis patients were allocated into an observation group, a medicine group and an EA group by simple randomization, with 32 cases in each group. Patients in the medicine group were treated with oral mecobalamine and prednisone acetate; patients in the EA group were treated with EA on the basis of the medicine treatment; while patients in the observation group were treated with acupoint sticking therapy with Mian Tan Gao (facial paralysis paste) plus EA. After 4-week treatment, the clinical efficacy, the adverse events, and the scores of House-Brackmann (H-B) facial nerve function grading scale, visual analog scale (VAS), clinical symptoms and signs, and facial disability index (FDI) were compared. Results: After 4-week treatment, the total effective rate was 96.9％ in the observation group, higher than 68.7％ in the medicine group and 75.0％ in the EA group (both P<0.05). After 4-week treatment, the scores of H-B grading scale, VAS and clinical symptoms and signs in the three groups dropped significantly compared with those before treatment, and the scores in the observation group were lower than those in the medicine group and EA group (all P<0.05). After 4-week treatment, the facial disability index-physical function (FDIP) in the FDI in the three groups increased significantly, with a higher value in the observation group compared with that in the medicine group and EA group (both P<0.05). The facial disability index-social function (FDIS) in the FDI dropped significantly, with a lower score in the observation group compared with that in the medicine group and EA group (both P<0.05). However, the comparisons of the items above between the medicine group and the EA group showed no statistical significance (all P>0.05). The between-group comparison of the adverse event across the three groups showed no statistical significance (P>0.05). Conclusion: Acupoint sticking therapy with Mian Tan Gao (facial paralysis paste) plus EA can decrease H-B grade, reduce pain severity and improve clinical symptoms and signs as well as the facial disability condition in peripheral facial paralysis patients. This method produced more significant efficacy compared with oral medicine and medicine plus EA.
