一項(xiàng)新的研究發(fā)現(xiàn)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抑制因子在艾滋病發(fā)病過(guò)程中,，扮演重要的角色,，而且它的作用方式與現(xiàn)有的抗病毒抑制劑都不同,，因此有助于研發(fā)出新型的抗艾滋病藥物,。這項(xiàng)研究的結(jié)果發(fā)表在4月20日的Cell中,。
德國(guó)Ulm大學(xué)的研究團(tuán)隊(duì)發(fā)現(xiàn)，一種血液分子片段VIRUS-INHIBITORY PEPTIDE,，病毒抑制肽,，縮寫為VIRIP，是效果廣泛的HIV-1抑制劑,。而且,，他們還證實(shí)這種片段中一些胺基酸變化，能夠?qū)⑺目共《灸芰μ嵘齼蓚€(gè)數(shù)量級(jí),。
VIRIP和它的衍生物還能有效抵抗藥物的HIV病毒株,，并因此使它們具有高的臨床開發(fā)潛力。
研究人員表示,，這些發(fā)現(xiàn)揭示出了抑制HIV病毒的一個(gè)新目標(biāo),，因此是一個(gè)重大的進(jìn)展。這個(gè)研究組還進(jìn)一步證實(shí),，HIV-1很難對(duì)這種肽片段產(chǎn)生抗性,，至少在培養(yǎng)的細(xì)胞中觀察到的結(jié)果如此。
研究人員還發(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,，而且在很高的濃度下也無(wú)毒。VIRIP的動(dòng)物試驗(yàn)?zāi)壳耙呀?jīng)大致完成,，研究人員希望今年能夠開始進(jìn)行人體試驗(yàn),。
（編譯/姜欣慧） (資料來(lái)源 : Bio.com)
英文原文鏈接：
原始出處:
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]
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.
