中国药物评价2024，Vol.41Issue(3)：222-232,11.
人干扰素α1b体外抗呼吸道病毒的药效学研究
Human Interferon α1b Broad-spectrum Viruses Pharmacodynamics Study in Vitro
摘要
Abstract
Objective:To evaluate the pharmacodynamic of human interferon α1b against broad-spectrum respiratory viruses in vitro.Methods:The toxicity of IFNα1b and positive control drugs on MDCK,U937,LLC-MK2,Hep-2,Vero E6,BHK-21,RD,A549 cells was detected by CPE method(cytopathic effect).Neuraminidase activity assay was used to detect the effects of IFNα1b and baloxavir on influenza virus strains CIV-H1N1/CNIC-1909(H1N1),A/kansas/14/2017(NYMCX-327)(H3N2)and B/Maryland/15/2016(NYM-CBX-69A)inhibitory effect;The inhibitory effects of IFNα1b,ribavirin and ibrutinib on influenza A strain(H1N1,A/PuertoRico/8/1934)and their inflammatory factors were detected by ELISA kit.Indirect immunofluorescence assay(IFA)was used to detect the inhibi-tory effect of IFNα1b and Ziresovir on respiratory syncytial virus(RSV A2)and the inhibitory effect of IFNα1b and ribavirin on human parainfluenza virus(HPIV3).The inhibitory effect of IFNα1b and NITD008 on DENV-2 virus,the inhibitory effect of IFNα1b and Vapen-davir on EV71 virus,the inhibitory effect of IFNα1b and CMX001 on human adenovirus type 3 virus strain(AdV3)and human adenovirus type 5 were detected inhibitory effect of virus strain(AdV5).The inhibition effect of IFNα1b and acyclovir on human herpes simplex virus type 1(HSV-1)was measured by plaque assay.Results:The CC50values of IFNα1b on MDCK cells were 479 572 U·mL-1.The EC50 values for inhibiting H1N1 were 4 265 U·mL-1.The selection index(SI)was 112.44.The EC50 for inhibiting H3N2 was 101 950 U·mL-1,and the SI was 4.70 The EC50 for inhibiting influenza B virus was 18 240 U·mL-1 and the SI was 18.50.The CC50 values of IFNα1b on U937 cells were more than 100 000 U·mL-1 and the EC50 values of H1N1 virus inhibition were 37 897 U·mL-1.The SI values were greater than 2.64 and the EC50 values for inhibiting inflammatory factor IP-10 were greater than 100 000 U·mL-1.The in-hibitory EC50 values of IL-8 were more than 100 000 U·mL-1.The CC50 values of IFNα1b on LLC-MK2 cells were more than 10 000 U·mL-1 and the EC50 values of HPIV3 virus inhibition were 3.92 U·mL-1.The CC50 values of IFNα1b against Hep 2 cells were more than 100 000 U·mL-1.The EC50values of RSV inhibition were 1661 U·mL-1 and the SI values were more than 60.2.The CC50 values of IFNα1b on BHK-21 cells were greater than 100 U·mL-1.The EC50 values of DENV-2 virus inhibition were 0.90 U·mL-1.The SI values were greater than 111.11.The CC50values of IFNα1b on RD cells were greater than 100 000 U·mL-1.The EC50 val-ues of EV71 inhibition were greater than 100 000 U·mL-1.The CC50 values of IFNα1b on A549 cells were greater than 100 000 U·mL-1 and the EC50 values of AdV3 virus inhibition were 100 000 U·mL-1.The EC50 was 100 000 U·mL-1.The CC50 values of IFNα1b for vero cell were more than 100 000 U·mL-1.The EC50 values for inhibiting HSV-1 virus were 6 898 U·mL-1 and the SI values were more than 14.5.Conclusion:At the cellular level in vitro,IFNα1b has inhibitory effects on influenza A viruses H1N1 and H3N2,influenza B viru-ses,RSV viruses,DENV-2 viruses,HPIV3 viruses and HSV-1 viruses.IFNα1b has no inhibitory effect on EV71 virus,AdV3 virus and AdV5 virus,and is expected to be a clinical drug for the prevention and treatment of upper respiratory tract viral infections.关键词
人干扰素α1b/体外/药效学/呼吸道病毒Key words
Human interferon α1b/Vitro/Pharmacodynamics/Respiratory viruses分类
医药卫生引用本文复制引用
刘琳琳,王晓波,苏畅,张廷辉,刘玉林,刘景会..人干扰素α1b体外抗呼吸道病毒的药效学研究[J].中国药物评价,2024,41(3):222-232,11.基金项目
吉林省科技发展计划基金项目(20160307028YY) （20160307028YY）
