title: Recombinant protein of heptad-repeat HR212, a stable fusion inhibitor with potent anti-HIV action in vitro.
abstract: HR212, a recombinant protein expressed in Escherichia coli, has been previously reported to inhibit HIV-1 membrane fusion at low nanomolar level. Here we report that HR212 is effective in blocking laboratory strain HIV-1(IIIB) entry and replication with EC(50) values of 3.92+/-0.62 and 6.59+/-1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1(KM018) with EC(50) values of 44.44+/-10.20 nM, as well as suppressing HIV-1-induced cytopathic effect with an EC(50) value of 3.04+/-1.20 nM. It also inhibited HIV-2(ROD) and HIV-2(CBL-20) entry and replication in the microM range. Notably, HR212 was highly effective against T20-resistant strains with EC(50) values ranging from 5.09 to 7.75 nM. Unlike T20, HR212 showed stability sufficient to inhibit syncytia formation in a time-of-addition assay, and was insensitive to proteinase K digestion. These results suggest that HR212 has great potential to be further developed as novel HIV-1 fusion inhibitor for treatment of HIV/AIDS patients, particularly for those infected by T20-resistant variants.
authors.affiliation: Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Wang
authors.forename: Liu-Meng
authors.initials: LM
authors.lastname: Yang
authors.forename: Chang-Mei
authors.initials: CM
authors.lastname: Liu
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D024882:Drug Resistance, Viral; D019286:Endopeptidase K / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020449:Repetitive Sequences, Amino Acid; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D011994:Recombinant Proteins; D019286:Endopeptidase K