Cell：人血中发现抗HIV天然成分
一项新的研究发现人类血液中能够有效抑制引发艾滋病的HIV-1病毒的一种天然成分。这种HIV-1抑制因子在艾滋病发病过程中，扮演重要的角色，而且它的作用方式与现有的抗病毒抑制剂都不同，因此有助于研发出新型的抗艾滋病药物。这项研究的结果发表在4月20日的Cell中。
德国Ulm大学的研究团队发现，一种血液分子片段VIRUS-INHIBITORY PEPTIDE，病毒抑制肽，缩写为VIRIP，是效果广泛的HIV-1抑制剂。而且，他们还证实这种片段中一些胺基酸变化，能够将它的抗病毒能力提升两个数量级。
VIRIP和它的衍生物还能有效抵抗药物的HIV病毒株，并因此使它们具有高的临床开发潜力。
研究人员表示，这些发现揭示出了抑制HIV病毒的一个新目标，因此是一个重大的进展。这个研究组还进一步证实，HIV-1很难对这种肽片段产生抗性，至少在培养的细胞中观察到的结果如此。
研究人员还发现初步的证据显示，一些肽衍生物在人类血清中稳定性很高，而且在很高的浓度下也无毒。VIRIP的动物试验目前已经大致完成，研究人员希望今年能够开始进行人体试验。
（编译/姜欣慧） (资料来源 : Bio.com)
英文原文链接：
原始出处:
Cell, Vol 129, 263-275, 20 April 2007
Article
Discovery and Optimization of a Natural HIV-1 Entry Inhibitor Targeting the gp41 Fusion Peptide
Jan Münch,1,9 Ludger Ständker,2,8,9 Knut Adermann,3,8 Axel Schulz,2 Michael Schindler,1 Raghavan Chinnadurai,1 Stefan Pöhlmann,4 Chawaree Chaipan,4 Thorsten Biet,5 Thomas Peters,5 Bernd Meyer,6 Dennis Wilhelm,6 Hong Lu,7 Weiguo Jing,7 Shibo Jiang,7 Wolf-Georg Forssmann,2,8,
and Frank Kirchhoff1,
1 Institute of Virology, University of Ulm, 89081 Ulm, Germany
2 IPF PharmaCeuticals GmbH, 30625 Hannover, Germany
3 VIRO Pharmaceuticals GmbH & Co. KG, 30625 Hannover, Germany
4 University of Erlangen-Nürnberg, Institute for Clinical and Molecular Virology and Nikolaus-Fiebiger-Center, 91054 Erlangen, Germany
5 Institute for Chemistry, University of Lübeck, 23538 Lübeck, Germany
6 Organic Chemistry, Faculty of Sciences, University of Hamburg, 20146 Hamburg, Germany
7 Lindsley F. Kimball Research Institute, The New York Blood Center, New York, NY 10021, USA
8 Hannover Medical School, Center of Pharmacology, 30625 Hannover, Germany
Corresponding author
Wolf-Georg Forssmann
wgforssmann@ipf-pharmaceuticals.de
Corresponding author
Frank Kirchhoff
frank.kirchhoff@uniklinik-ulm.de
Summary
A variety of molecules in human blood have been implicated in the inhibition of HIV-1. However, it remained elusive which circulating natural compounds are most effective in controlling viral replication in vivo. To identify natural HIV-1 inhibitors we screened a comprehensive peptide library generated from human hemofiltrate. The most potent fraction contained a 20-residue peptide, designated VIRUS-INHIBITORY PEPTIDE (VIRIP), corresponding to the C-proximal region of α1-antitrypsin, the most abundant circulating serine protease inhibitor. We found that VIRIP inhibits a wide variety of HIV-1 strains including those resistant to current antiretroviral drugs. Further analysis demonstrated that VIRIP blocks HIV-1 entry by interacting with the gp41 fusion peptide and showed that a few amino acid changes increase its antiretroviral potency by two orders of magnitude. Thus, as a highly specific natural inhibitor of the HIV-1 gp41 fusion peptide, VIRIP may lead to the development of another class of antiretroviral drugs.
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