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...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.展开更多
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)+3 种基金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)
文摘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.
