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

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

  • BMC Microbiol. 2015 Dec 2:15:274. doi: 10.1186/s12866-015-0605-3.
Ru Bai 1,  Xing-Jie Zhang 2,  Yan-Li Li 3,  Jing-Ping Liu 4,  Hong-Bin Zhang 5,  Wei-Lie Xiao 6,  Jian-Xin Pu 7,  Han-Dong Sun 8,  Yong-Tang Zheng 9,  Li-Xin Liu 10
Affiliations

Affiliations

  • 1 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China. [email protected].
  • 2 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. [email protected].
  • 3 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China. [email protected].
  • 4 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. [email protected].
  • 5 Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P. R. China. [email protected].
  • 6 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. [email protected].
  • 7 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. [email protected].
  • 8 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, P. R. China. [email protected].
  • 9 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. [email protected].
  • 10 Sun Yat-Sen University, Guangzhou, 510275, P. R. China. [email protected].
PMID: 26630969 DOI: 10.1186/s12866-015-0605-3
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.

Figures
Products