Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1 Predominantly Circulating in China  

作　　者：WANG Yan CURRELI Francesca XU Wei Si LI Zhen Peng KONG De Sheng REN Li HONG Kun Xue JIANG Shi Bo SHAO Yi Ming DEBNATH Asim K MA Li Ying 

机构地区：[1]State Key Laboratory of Infectious Disease Prevention and Control,National Center for AIDS/STD Control and Prevention,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,Chinese Center for Disease Control and Prevention,Beijing 102206,China [2]State Key Laboratory of Infectious Disease Prevention and Control,National Institute for Communicable Disease Control and Prevention,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,Chinese Center for Disease Control and Prevention,Beuhing 102206,China [3]Laboratory of Molecular Modeling and Drug Design,Lindsley F.Kimball Research Institute of the New York Blood Center,New York 10065,USA [4]Key Laboratory of Medical Molecular Virology of Ministries of Education and Health,Shanghai Medical College and Institute of Medical Microbiology,Fudan University,Shanghai 200032,China

出　　处：《Biomedical and Environmental Sciences》2017年第6期398-406,共9页生物医学与环境科学（英文版）

基　　金：supported by the National Natural Science Foundation of China(NSFC,No.81261120384);the Key Project of the State Key Laboratory for Infectious Diseases Prevention and Control(SKLID,No.2011SKLID102);the Ministry of Science and Technology of China(2012ZX10001-002);the European Research Infrastructures for Poverty Related Diseases(312661);by funds from NIH Grant RO1 AI104416(AKD);the New York Blood Center(AKD)

摘　　要：Objective New rationally designed i,i＋7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. Methods The antiviral activity of three i,i＋7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRFOI_AE isolates was evaluated in peripheral blood mononuclear cells （PI3MCs）. The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. Results We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication （ICso） in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the ICs0s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Conclusion Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.Objective New rationally designed i,i＋7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. Methods The antiviral activity of three i,i＋7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRFOI_AE isolates was evaluated in peripheral blood mononuclear cells （PI3MCs）. The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. Results We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication （ICso） in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the ICs0s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Conclusion Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.

关 键 词：Hydrocarbon-stapled peptide HIV-1 CRF07 BC CRFOI_AE Antiviral activity 

分 类 号：R512.91[医药卫生—内科学]