Mechanisms and modifications of naturally occurring host defense peptides for anti-HIV microbicide development.
Mechanisms and modifications of naturally occurring host defense peptides for anti-HIV microbicide development.
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DOI：
10.2174/157016212799304580
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发表时间：
2012-01-01
影响因子：
1
通讯作者：
Cole AM
中科院分区：
文献类型：
--
作者：
Eade CR;Wood MP;Cole AM
尽管艾滋病毒感染的治疗取得了进展，但艾滋病毒的异性传播仍然很高，预防艾滋病毒感染的疫苗也没有取得成果。另一方面，阴道杀微生物剂已显示出预防艾滋病毒的巨大潜力，并且已经筛选了多种化合物作为抗艾滋病毒杀微生物剂的活性和安全性。其中包括天然存在的宿主防御肽，来自不同谱系的具有内在抗病毒活性的小肽。具有抗 HIV 活性的天然宿主防御肽是阴道杀菌剂开发的有希望的候选者。它们的结构差异和伴随的机制多样性提供了广泛的抑制剂，其抗病毒活性几乎可以在艾滋病毒生命周期的每个阶段发挥作用。此外，肽修饰已被探索作为提高宿主防御肽的抗HIV活性的方法。基于结构和序列的改变在提高抗HIV肽的效力和特异性方面取得了不同程度的成功。总体而言，已经发现或设计了能够抑制 HIV 的肽，其治疗指数>1000，这鼓励了它们向临床试验的进展。在这里，我们回顾了天然存在的抗 HIV 宿主防御肽，展示了其机制多样性的广度，并探索增强和优化其活性的方法，以加快其开发为安全有效的抗 HIV 阴道杀微生物剂。
Despite advances in the treatment of HIV infection, heterosexual transmission of HIV remains high, and vaccines to prevent HIV acquisition have been unfruitful. Vaginal microbicides, on the other hand, have demonstrated considerable potential for HIV prevention, and a variety of compounds have been screened for their activity and safety as anti-HIV microbicides. Among these are the naturally occurring host defense peptides, small peptides from diverse lineages with intrinsic antiviral activity. Naturally occurring host defense peptides with anti-HIV activity are promising candidates for vaginal microbicide development. Their structural variance and accompanying mechanistic diversity provide a wide range of inhibitors whose antiviral activity can be exerted at nearly every stage of the HIV lifecycle. Additionally, peptide modification has been explored as a method for improving the anti-HIV activity of host defense peptides. Structure- and sequence-based alterations have achieved varying success in improving the potency and specificity of anti-HIV peptides. Overall, peptides have been discovered or engineered to inhibit HIV with therapeutic indices of >1000, encouraging their advancement toward clinical trials. Here we review the naturally occurring anti-HIV host defense peptides, demonstrating their breadth of mechanistic diversity, and exploring approaches to enhance and optimize their activity in order to expedite their development as safe and effective anti-HIV vaginal microbicides.