Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1 Predominantly Circulating in China.
- Author:
Yan WANG
1
;
Francesca CURRELI
2
;
Wei Si XU
1
;
Zhen Peng LI
2
;
De Sheng KONG
1
;
Li REN
1
;
Kun Xue HONG
1
;
Shi Bo JIANG
3
;
Yi Ming SHAO
1
;
Asim K DEBNATH
4
;
Li Ying MA
1
Author Information
- Publication Type:Journal Article
- Keywords: Antiviral activity; CRF01_AE; CRF07_BC; HIV-1; Hydrocarbon-stapled peptide
- MeSH: Amino Acid Sequence; Anti-HIV Agents; chemistry; pharmacology; China; epidemiology; HIV Envelope Protein gp120; genetics; metabolism; HIV Infections; epidemiology; virology; HIV-1; drug effects; genetics; Humans; Peptides, Cyclic; administration & dosage; pharmacology; Phylogeny
- From: Biomedical and Environmental Sciences 2017;30(6):398-406
- CountryChina
- Language:English
-
Abstract:
OBJECTIVENew 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.
METHODSThe antiviral activity of three i,i+7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood mononuclear cells (PBMCs). The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells.
RESULTSWe 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 (IC50) 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 IC50s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67.
CONCLUSIONHydrocarbon-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.