3月18日,法国国家科研中心宣布,该机构的研究人员日前合成了一种分子,能够阻止艾滋病病毒在细胞间传播。
该中心当天发表公报说,虽然人类在抗击艾滋病方面取得了不小的进步,但这种传染病每年仍会夺走上百万人的生命。科研中心研究人员从一种名为DC―SIGN的蛋白质入手进行研究,后者存在于免疫系统的树突细胞表面,处在与外界病毒接触的最前线,在艾滋病病毒的传播初期发挥着重要作用。
研究人员说,在正常情况下,DC―SIGN能通过辨别病原体表面独有的寡糖,将病毒拦截下来。随后,树突细胞就会发挥作用,它先把病毒分解,再将其携带到淋巴结上,从而开启免疫系统抵御病毒。不过,艾滋病病毒利用这一特性,在“摆渡”到淋巴结后向淋巴TCD4+细胞发起攻击,从而达到传播的目的。
根据这一机理,法国国家科研中心合成一种分子,这种分子可以阻止艾滋病病毒与淋巴TCD4+的接触,从而预防艾滋病病毒传播。研究人员介绍说,这种分子具有高度的可溶性、低毒性及持久性等优点。这项研究下一步将进入动物实验阶段。
原文出处:
ACS Chem. Biol. DOI: 10.1021/cb900216e
Inhibition of DC-SIGN-Mediated HIV Infection by a Linear Trimannoside Mimic in a Tetravalent Presentation
Sara Sattin?, Anna Daghetti?, Michel Thpaut?#, Angela Berzi, Macarena Snchez-Navarro§, Georges Tabarani???, Javier Rojo§, Franck Fieschi???, Mario Clerici? and Anna Bernardi?*
HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this context, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is a promising therapeutic target. Herein we show the ability of a new tetravalent dendron containing four copies of a linear trimannoside mimic to inhibit the trans HIV infection process of CD4+ T lymphocytes at low micromolar range. This compound presents a high solubility in physiological media, a neglectable cytotoxicity, and a long-lasting effect and is based on carbohydrate-mimic units. Notably, the HIV antiviral activity is independent of viral tropism (X4 or R5). The formulation of this compound as a gel could allow its use as topical microbicide.