de la Guardia Carolina, Quijada Mario, Lleonart Ricardo
Center of Cellular and Molecular Biology of Diseases, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Building 219, Ciudad del Saber, Apartado 0843-01103, Panamá, Panama.
Department of Biotechnology, Acharya Nagarjuna University, Guntur, India.
Adv Virol. 2017;2017:1827341. doi: 10.1155/2017/1827341. Epub 2017 Sep 10.
Dengue virus is a growing public health threat that affects hundreds of million peoples every year and leave huge economic and social damage. The virus is transmitted by mosquitoes and the incidence of the disease is increasing, among other causes, due to the geographical expansion of the vector's range and the lack of effectiveness in public health interventions in most prevalent countries. So far, no highly effective vaccine or antiviral has been developed for this virus. Here we employed phage display technology to identify peptides able to block the DENV2. A random peptide library presented in M13 phages was screened with recombinant dengue envelope and its fragment domain III. After four rounds of panning, several binding peptides were identified, synthesized, and tested against the virus. Three peptides were able to block the infectivity of the virus while not being toxic to the target cells. Blind docking simulations were done to investigate the possible mode of binding, showing that all peptides appear to bind domain III of the protein and may be mostly stabilized by hydrophobic interactions. These results are relevant to the development of novel therapeutics against this important virus.
登革病毒对公共卫生构成的威胁日益严重，每年影响数亿人，并造成巨大的经济和社会损失。该病毒通过蚊子传播，除其他原因外，由于病媒范围的地理扩张以及大多数流行国家公共卫生干预措施缺乏成效，该疾病的发病率正在上升。到目前为止，尚未针对这种病毒开发出高效疫苗或抗病毒药物。在此，我们利用噬菌体展示技术来鉴定能够阻断登革2型病毒（DENV2）的肽段。用重组登革病毒包膜及其结构域III片段筛选呈现在M13噬菌体中的随机肽库。经过四轮淘选，鉴定出几种结合肽，进行合成并针对该病毒进行测试。三种肽能够阻断病毒的感染性，同时对靶细胞无毒。进行了分子对接模拟以研究可能的结合模式，结果表明所有肽似乎都与该蛋白的结构域III结合，并且可能主要通过疏水相互作用而稳定。这些结果与开发针对这种重要病毒的新型疗法相关。
