SJP-L-5, a novel small-molecule compound, inhibits HIV-1 infection by blocking viral DNA nuclear entry

BMC Microbiology

Research Article

Yan-Li Li¹  Ru Bai¹  Yong-Tang Zheng²  Xing-Jie Zhang²  Hong-Bin Zhang³  Wei-Lie Xiao⁴  Jian-Xin Pu⁴  Jing-Ping Liu⁴  Han-Dong Sun⁴  Li-Xin Liu⁵ 

[1] College of Life Sciences, University of Chinese Academy of Sciences, 100049, Beijing, P. R. China;Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and the Kunming Institute of Zoology of the Chinese Academy of Sciences, 650223, Kunming, P. R. China;Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education, School of Chemical Science and Technology, Yunnan University, 650091, Kunming, P. R. China;State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 650204, Kunming, P. R. China;Sun Yat-Sen University, 510275, Guangzhou, P. R. China;

关键词: HIV-1;    Pre-integration complex;    Nuclear entry;    Capsid;    SJP-L-5;   

DOI  :  10.1186/s12866-015-0605-3

 received in 2015-01-19, accepted in 2015-11-24,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundSmall-molecule compounds that inhibit human immunodeficiency virus type 1 (HIV-1) infection can be used not only as drug candidates, but also as reagents to dissect the life cycle of the virus. Thus, it is desirable to have an arsenal of such compounds that inhibit HIV-1 infection by various mechanisms. Until now, only a few small-molecule compounds that inhibit nuclear entry of viral DNA have been documented.ResultsWe identified a novel, small-molecule compound, SJP-L-5, that inhibits HIV-1 infection. SJP-L-5 is a nitrogen-containing, biphenyl compound whose synthesis was based on the dibenzocyclooctadiene lignan gomisin M2, an anti-HIV bioactive compound isolated from Schisandra micrantha A. C. Smith. SJP-L-5 displayed relatively low cytotoxicity (50 % cytoxicity concentrations were greater than 200 μg/ml) and high antiviral activity against a variety of HIV strains (50 % effective concentrations (EC50)) of HIV-1 laboratory-adapted strains ranged from 0.16–0.97 μg/ml; EC50s of primary isolates ranged from 1.96–5.33 μg/ml). Analyses of the viral DNA synthesis indicated that SJP-L-5 specifically blocks the entry of the HIV-1 pre-integration complex (PIC) into the nucleus. Further results implicated that SJP-L-5 inhibits the disassembly of HIV-1 particulate capsid in the cytoplasm of the infected cells.ConclusionsSJP-L-5 is a novel small-molecule compound that inhibits HIV-1 nuclear entry by blocking the disassembly of the viral core.

【 授权许可】

CC BY   
© Bai et al. 2015