德國科學家在人體血液中發(fā)現(xiàn)一種縮氨酸,，試驗發(fā)現(xiàn)它可以阻止艾滋病病毒附著、侵入人體細胞,。這一發(fā)現(xiàn)為抗艾滋病藥物的開發(fā)提供了新途徑,。
據(jù)德新社近日報道，德國烏爾姆大學研究人員對人體血液中的大量成分進行分析篩選,，最終找到了這種縮氨酸,。研究人員將它命名為病毒抑制縮氨酸VIRIP。VIRIP可以干擾艾滋病病毒HIV-1型病毒的表面蛋白GP41,，使其不能發(fā)揮作用,，從而阻止HIV-1病毒附著到人體細胞上。
對于VIRIP的動物試驗?zāi)壳耙呀?jīng)基本完成,，研究人員希望今年能夠開始人體試驗,。有關(guān)研究成果刊登在最新一期《細胞》雜志上。
一項新的研究確定出了人類血液中能夠有效抑制引發(fā)艾滋病的HIV-1病毒的一種天然成分,。這種HIV-1抑制銀子可能在HIV向艾滋病發(fā)作過渡過程中起到一定的作用,，而且它的作用方式與現(xiàn)有的抗病毒抑制劑都不同，因此可能導(dǎo)致人們開發(fā)出新型的抗艾滋病藥物,。這項研究的結(jié)果發(fā)表在4月20日的Cell雜志上,。
德國Ulm大學的這個研究隊伍發(fā)現(xiàn),，比較豐富的一種血液分子片段(他們命名為VIRUS-INHIBITORY PEPTIDE,，病毒抑制肽，縮寫VIRIP)能夠充當廣泛的HIV-1抑制劑,。而且,，他們還證實這種片段中一些氨基酸的變化能夠?qū)⑺目共《灸芰μ嵘齼蓚€數(shù)量級,。
VIRIP和它的衍生物還能有效抵抗藥物康熙HIV株，并因此使它們具有高的臨床開發(fā)潛力,。
研究人員評價說,，這些發(fā)現(xiàn)揭示出了抑制HIV病毒的一個新靶標，因此是一個重大的進展,。這個研究組還進一步證實HIV-1很難對這種肽片段產(chǎn)生抗性,，至少在培養(yǎng)的細胞中是這樣。而且他們的同事還發(fā)現(xiàn)初步的證據(jù)顯示一些肽衍生物在人類血清中穩(wěn)定性很高,，并且在很高的濃度下也無毒,。
原始出處:
Copyright © 2007 Cell Press. All rights reserved.
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
[email protected]
Corresponding author
Frank Kirchhoff
[email protected]
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.
