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【bio-news】新药可阻断HIV锚定在宿主细胞之上
据一项新的研究报道，一种基于由人体产生的自然化合物的新药可中断HIV感染的最早阶段。 此药也许能够减慢该病毒对抗逆转录病毒药物的抵抗力—这是一个全世界范围内的日益严重的问题。 该药被称作VIR-576，它会与HIV将其外膜的“粘性”端(即融合肽)插入宿主细胞的能力发生相互作用。 VIR-576的这一阻断融合肽的能力使其与其它的HIV药物迥然不同。 这些发现第一次证明，一种在身体中发现的自然化合物的衍生物可以抗HIV;这也是抑制融合肽可通过防止病毒与宿主细胞之间的直接互动而中止HIV在人体内复制的第一个证据。 艾滋病毒的外包层或“包膜”可通过将其膜与某个宿主细胞融合以启动传染来帮助艾滋病毒存活和扩散。 融合肽在这一过程中扮演着一个关键性的角色。
大多数的包膜病毒(其中包括流感病毒、腮腺炎病毒、麻疹病毒、乙肝病毒、丙肝病毒、伊波拉病毒和SARS病毒)也会利用其融合肽。 因此，VIR-576可有效对抗HIV早期感染的发现提示，人们有可能研发出类似的抑制剂来对抗其它的危险病毒。 此外，融合肽几乎不能耐受基因的改变，因此该病毒很可能难以出现对VIR-576的抵抗力。 在本研究中，18名暂时没有接受任何抗逆转录病毒治疗的感染了HIV的病人接受了为期10天的三种不同剂量的该新药的治疗。 研究人员发现，病人对该新药有着良好的耐受性，并在服用最高剂量该药的时候可将病毒的平均载量(这是对血液中活性HIV量的一种测定)减少95%。 然而，这一新药确实存在着某些缺点。 由于VIR-576是一种肽且必须注射给药，因此其使用将很昂贵且不方便。 这促使了Kirchhoff及其同事开始搜寻一种与VIR-576的作用方式一样，但有着可廉价生产且能口服等优点的小分子。
New drug blocks anchoring of HIV to host cells
A new drug based on a natural compound produced by the human body halts one of the earliest stages of HIV infection, reports a new study. The drug may be able to slow down emerging resistance of the virus to antiretroviral drugs, a growing problem worldwide. Called VIR-576, the drug interacts with HIV’s ability to insert the "sticky" end of its outer membrane -- the fusion peptide -- into the host cell. This ability to block fusion peptides makes VIR-576 very different from other HIV drugs. The findings show for the first time that a derivative of a natural compound found in the body has proven effective against HIV, and the first evidence that inhibiting fusion peptides can stall HIV replication in humans by preventing direct interaction between the virus and host cells. The outer wrapping or “envelope” of the AIDs virus helps it survive and spread by fusing its membrane with a host cell membrane to initiate infection. Fusion peptides play a critical role in this process.
Fusion peptides are also used by most enveloped viruses, including Influenza, Mumps, Measles, Hepatitis B, Hepatitis C, Ebola, and SARS viruses. So, the discovery that VIR-576 can effectively fight early HIV infection suggests that it may be possible to develop similar inhibitors against other dangerous viruses. Moreover, fusion peptides can hardly tolerate genetic changes, so it will likely be difficult for the virus to develop resistance to VIR-576. In the study, 18 HIV-infected patients who temporarily were not on any other antiretroviral therapy were treated for 10 days with three different doses of the new drug. The researchers found that the drug was well tolerated and reduced the average viral load (a measurement of the amount of active HIV the blood) by 95 percent, when taken at the highest dose. However, this new drug does have some drawbacks. Because VIR-576 is a peptide and must be given through injections, it will be costly and inconvenient to use. This has prompted Kirchhoff and colleagues to start hunting for a small molecule that works just like VIR-576 but with the advantage that it could be made cheaply and given orally.
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Article: "Short-term Monotherapy in HIV-infected Patients with a Virus Entry Inhibitor Against the gp41 Fusion Peptide," by W.-G. Forssmann; Y.-H. The; M. Stoll; K. Adermann; A. Busmann; J. Hirsch; D. Meyer-Olson; L. St?ndker; R.E. Schmidt at Hannover Medical School in Hannover, Germany; W.-G. Forssmann; K. Adermann; A. Busmann; J. Hirsch at VIRO Pharmaceuticals GmbH & Co. KG in Hannover, Germany; U. Albrecht at Mediconomics GmbH in Hannover, Germany; K. Barlos at University of Patras in Rion-Patras, Greece; A. Canáles-Mayordomo; Giménez-Gallego; J. Jiménez-Barbero at Centro de Investigaciones Biológicas, CSIC in Madrid, Spain; J. Münch; F. Kirchhoff at University Hospital of Ulm in Ulm, Germany; J. Pérez-Castells at Universidad San Pablo CEU in Madrid, Spain; W.-G. Forssmann; K. Adermann; K. Hirsch at Pharis Biotec GmbH in Hannover, Germany; K. Barlos at CBL-Patras in Patras, Greece.
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作者:admin@医学,生命科学 2010-12-25 12:22
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