人干扰素α1b体外抗SARS-CoV-2 Omicron株的药效

Pharmacodynamics of human interferonα1b against severe acute respiratory syndrome coronavirus 2 Omicron strain in vitro

目的评价人干扰素(interferon,IFN)α1b体外抗严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)Omicron株的药效。方法采用CCK-8法检测人IFNα1b原液、人IFNα1b滴眼液、人IFNα1b喷雾剂、瑞德西韦共4种药物的细胞毒性;qPCR法检测人IFNα1b对SARS-CoV-2 Omicron株(BA.5/BA.2/BA.1)的抑制效果。结果最高浓度(1×107IU/mL)人IFNα1b原液和最高浓度(150μmol/L)瑞德西韦对Vero细胞未达到半数细胞毒性;人IFNα1b滴眼液和人IFNα1b喷雾剂的半数毒性浓度(CC50)分别为29958和37550 IU/mL,对Vero细胞具有毒性。人IFNα1b提前孵育2 h后再攻毒,对BA.1、BA.2、BA.5株的半数有效浓度(EC_(50))分别为9.30、13.38、12.33 IU/mL,瑞德西韦分别为0.3147、0.2910、0.3003μmol/L。人IFNα1b与病毒同时孵育,对BA.1、BA.2、BA.5株的EC_(50)分别为19.68、10.91、18.84 IU/mL,对照药瑞德西韦分别为0.3205、0.2744、0.3041μmol/L。结论在体外细胞水平上,极低活性的人IFNα1b即可对SARS-CoV-2 Omicron株具有较好的抑制作用,有望成为治疗SARS-CoV-2 Omicron株感染的临床特效药。

Objective To evaluate the pharmacodynamics of human interferon(IFN)α1b against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron strain in vitro.Methods Total four drugs human IFNα1b bulk,human IFNα1b eye drops,human IFNα1b spray and Remdesivir were detected for cytotoxicity by CCK-8 assay.The inhibitory effect of human IFNα1b on SARS-CoV-2 Omicron strains(BA.5/BA.2/BA.1)was determined by qPCR.Results Human IFNα1b bulk of the maximum concentration(1×10~7IU/mL)and Remdesivir of the maximum concentration(150μmol/L)did not achieve half cytotoxicity to Vero cells;The median cytotoxicity concentrations(CC50)of human IFNα1b eye drops and human IFNα1b sprays were 29958 and 37550 IU/mL,respectively,showing toxicity to Vero cells.The median effective concentrations(EC_(50))of human IFNα1b against virus strains BA.1,BA.2 and BA.5 after incubation for 2 h in advance were 9.30,13.38 and 12.33 IU/mL and those of Remdesivir were 0.3147,0.2910 and0.3003μmol/L.When incubation with virus simultaneously,the EC_(50)of human IFNα1b to BA.1,BA.2 and BA.5 were19.68,10.91 and 18.84 IU/mL and those of the control drug Remdesivir were 0.3205,0.2744 and 0.3041μmol/L,respectively.Conclusion At the cell level in vitro,human IFNα1b of very low activity showed a good inhibitory effect on SARS-CoV-2 Omicron strain,which was expected to be a clinical specific drug for the treatment of SARS-CoV-2 Omicron strain infection.