title: SJP-L-5, a novel small-molecule compound, inhibits HIV-1 infection by blocking viral DNA nuclear entry.
abstract: BACKGROUND
  Small-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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  SJP-L-5 is a novel small-molecule compound that inhibits HIV-1 nuclear entry by blocking the disassembly of the viral core.
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China. bairu10@mails.ucas.ac.cn.
authors.forename: Ru
authors.initials: R
authors.lastname: Bai
authors.affiliation: 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, Kunming, 650223, P. R. China. kmhz123@163.com.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China. lyh178@163.com.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. liujp72@163.com.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P. R. China. zhanghb@ynu.edu.cn.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. xwl@mail.kib.ac.cn.
authors.forename: Wei-Lie
authors.initials: WL
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. pujianxin@mail.kib.ac.cn.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Pu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. hdsun@mail.kib.ac.cn.
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Sun
authors.affiliation: 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, Kunming, 650223, P. R. China. zhengyt@mail.kiz.ac.cn.
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.affiliation: Sun Yat-Sen University, Guangzhou, 510275, P. R. China. liulixin@mail.sysu.edu.cn.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D032141:Schisandra / Q000737:chemistry; D016662:Virus Integration / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D010936:Plant Extracts