SJP-L-5 inhibits HIV-1 polypurine tract primed plus-strand DNA elongation, indicating viral DNA synthesis initiation at multiple sites under drug pressure
Zhang, Xing-Jie1,2,3; Wang, Rui-Rui1,4; Chen, Huan1,3; Luo, Rong-Hua1; Yang, Liu-Meng1; Liu, Jing-Ping5; Sun, Han-Dong5; Zhang, Hong-Bin2; Xiao, Wei-Lie2,5; Zheng, Yong-Tang1,3,6
2018-02-07
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume8Issue:1Pages:2574
Abstract

In a previous study the small molecule SJP-L-5 that inhibits HIV replication, has been shown to block uncoating of the viral capsid. Continued study showed that SJP-L-5 might hinder HIV capsid uncoating by blocking the completion of reverse transcription. However, to date, the mechanism has not been fully elucidated. Here, the effects of SJP-L-5 for reverse transcription were explored via quantitative PCR, DIG-labelled ELISA, fluorescent resonance energy transfer, and Southern blot assays. We also analyzed the resistance profile of this compound against reverse transcriptase. Our results show that SJP-L-5 preferentially inhibits PPT primed plus-strand DNA synthesis (EC50 = 13.4 +/- 3.0 mu M) over RNA primed minus-strand DNA synthesis (EC50 > 3,646 mu M), resulting in formation of five segmented plus-strand DNA and loss of HIV DNA flap, suggesting failure of both nuclear import and integration. Moreover, resistance study evidenced that SJP-L-5 requires the amino acid residues Val108 and Tyr181 to exert an inhibitory effect. These results indicate SJP-L-5 as a new non-nucleoside reverse transcriptase inhibitor that inhibits HIV-1 polypurine tract primed plus-strand DNA synthesis, initiating HIV-1 down-stream plus-strand DNA synthesis at multiple sites under drug pressure.

DOI10.1038/s41598-018-20954-5
Language英语
WOS IDWOS:000424318700046
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/60459
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Key Lab Bioact Peptides Yunnan Province, Kunming 650223, Yunnan, Peoples R China
2.Yunnan Univ, Key Lab Med Chem Nat Resource, Minist Educ & Yunnan Prov, Kunming 650091, Yunnan, Peoples R China
3.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650204, Yunnan, Peoples R China
4.Yunnan Univ Tradit Chinese Med, Coll Pharmaceut Sci, Kunming 650500, Yunnan, Peoples R China
5.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
6.Soochow Univ, Coll Pharmaceut Sci, KIZ SU Joint Lab Anim Models & Drug Dev, Suzhou 215006, Jiangsu, Peoples R China
Recommended Citation
GB/T 7714
Zhang, Xing-Jie,Wang, Rui-Rui,Chen, Huan,et al. SJP-L-5 inhibits HIV-1 polypurine tract primed plus-strand DNA elongation, indicating viral DNA synthesis initiation at multiple sites under drug pressure[J]. SCIENTIFIC REPORTS,2018,8(1):2574.
APA Zhang, Xing-Jie.,Wang, Rui-Rui.,Chen, Huan.,Luo, Rong-Hua.,Yang, Liu-Meng.,...&Zheng, Yong-Tang.(2018).SJP-L-5 inhibits HIV-1 polypurine tract primed plus-strand DNA elongation, indicating viral DNA synthesis initiation at multiple sites under drug pressure.SCIENTIFIC REPORTS,8(1),2574.
MLA Zhang, Xing-Jie,et al."SJP-L-5 inhibits HIV-1 polypurine tract primed plus-strand DNA elongation, indicating viral DNA synthesis initiation at multiple sites under drug pressure".SCIENTIFIC REPORTS 8.1(2018):2574.
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