Sifuvirtide, a potent HIV fusion inhibitor peptide

	Sifuvirtide, a potent HIV fusion inhibitor peptide
	Wang RR 1; Yang LM 1; Wang YH 1; Pang W 1,2; Tam SC 3; Tien P 2; Zheng YT*1; zhengyt@mail.kiz.ac.cn
	2009
发表期刊	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN	0006-291X
卷号	382 期号:3 页码:540-544
合作性质	其它
摘要	Enfuvirtide (ENF) is currently the only FDA approved HIV fusion inhibitor in clinical use. Searching for more drugs in this category with higher efficacy and lower toxicity seems to be a logical next step. In line with this objective, a synthetic peptide with 36 amino acid residues, called Sifuvirtide (SFT), was designed based on the crystal structure of gp41. In this study, we show that SFT is a potent anti-HIV agent with relatively low cytotoxicity. SFT was found to inhibit replication of all tested HIV strains. The effective concentrations that inhibited 50% viral replication (EC(50)), as determined in all tested strains, were either comparable or lower than benchmark values derived from well-known anti-HIV drugs like ENF or AZT, while the cytotoxic concentrations causing 50% cell death (CC(50)) were relatively high, rendering it an ideal anti-HIV agent. A GST-pull down assay was performed to confirm that SFT is a fusion inhibitor. Furthermore, the activity of SFT on other targets in the HIV life cycle was also investigated, and all assays showed negative results. To further understand the mechanism of action of HIV peptide inhibitors, resistant variants of HIV-1(IIB) were derived by serial virus passage in the presence of increasing doses of SFT or ENF. The results showed that there was cross-resistance between SFT and ENF.
关键词	Sifuvirtide Enfuvirtide Fusion Inhibitor Hiv-1 Anti-hiv Agents
资助者	This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript. ; This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript. ; This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript. ; This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript.
收录类别	SCI
语种	英语
资助者	This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript. ; This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript. ; This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript. ; This work was supported in part by grants from the CAS (KSCX1- YW-R-15, KSCX1-YW-R-24) and 973 Program (2006CB504302, 2006CB504208, 2009CB5223006). We would like to acknowledge the MRC AIDS Research Project and the NIH AIDS Research and Ref- erence Reagent Program for providing cell lines and viruses. We would like to thank Dr. Jing-Zong Qi and Mr. Qing Liang for discus- sions and suggestions and thank Ms. Xin Chen for her review of the manuscript.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/4673
专题	科研部门_分子免疫药理学（郑永唐）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	zhengyt@mail.kiz.ac.cn
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 2.Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China 3.Department of Physiology, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
推荐引用方式 GB/T 7714	Wang RR,Yang LM,Wang YH,et al. Sifuvirtide, a potent HIV fusion inhibitor peptide[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2009,382(3):540-544.
APA	Wang RR.,Yang LM.,Wang YH.,Pang W.,Tam SC.,...&zhengyt@mail.kiz.ac.cn.(2009).Sifuvirtide, a potent HIV fusion inhibitor peptide.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,382(3),540-544.
MLA	Wang RR,et al."Sifuvirtide, a potent HIV fusion inhibitor peptide".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 382.3(2009):540-544.

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