Eade Colleen R, Wood Matthew P, Cole Alexander M
Department of Molecular Biology and Microbiology, Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL 32816, USA.
Curr HIV Res. 2012 Jan 1;10(1):61-72. doi: 10.2174/157016212799304580.
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.
尽管在HIV感染治疗方面取得了进展，但HIV的异性传播率仍然很高，预防HIV感染的疫苗也未取得成效。另一方面，阴道杀菌剂已显示出在预防HIV方面具有相当大的潜力，并且已经筛选了多种化合物作为抗HIV杀菌剂的活性和安全性。其中包括天然存在的宿主防御肽，这些来自不同谱系的小肽具有内在的抗病毒活性。具有抗HIV活性的天然宿主防御肽是开发阴道杀菌剂的有希望的候选者。它们的结构差异和相应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HIV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抗HIV活性的一种方法。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，已发现或设计出治疗指数>1000的抑制HIV的肽，这鼓励它们朝着临床试验方向发展。在这里，我们综述了天然存在的抗HIV宿主防御肽，展示了它们机制多样性的广度，并探索增强和优化其活性的方法，以加快它们作为安全有效的抗HIV阴道杀菌剂的开发。
