Zhao Hanjun, Zhou Jie, Zhang Ke, Chu Hin, Liu Dabin, Poon Vincent Kwok-Man, Chan Chris Chung-Sing, Leung Ho-Chuen, Fai Ng, Lin Yong-Ping, Zhang Anna Jin-Xia, Jin Dong-Yan, Yuen Kwok-Yung, Zheng Bo-Jian
Department of Microbiology, The University of Hong Kong, Hong Kong, China.
School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
Sci Rep. 2016 Feb 25;6:22008. doi: 10.1038/srep22008.
A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.
迫切需要一种安全、高效且广谱的抗病毒药物来对抗新出现的呼吸道病毒。鉴于β-防御素具有广泛的抗病毒活性，我们测试了11种源自小鼠β-防御素-4的肽的抗病毒活性，发现一种短肽P9在体外和体内对多种呼吸道病毒均表现出强大的广谱抗病毒作用，这些病毒包括甲型流感病毒H1N1、H3N2、H5N1、H7N7、H7N9、严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV）。P9的抗病毒活性归因于其与病毒糖蛋白的高亲和力结合以及其组成中丰富的碱性氨基酸。通过病毒表面糖蛋白结合病毒颗粒后，P9与病毒一起通过内吞作用进入细胞，并阻止内体酸化，从而阻断膜融合及随后的病毒RNA释放。这项研究为开发具有广谱抗病毒活性的新型预防和治疗药物铺平了道路。
