Hoffmann Julia, Schneider Carola, Heinbockel Lena, Brandenburg Klaus, Reimer Rudolph, Gabriel Gülsah
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany.
Leibniz-Center for Medicine and Biosciences, Research Center Borstel, Parkallee 35, 23845 Borstel, Germany.
Antiviral Res. 2014 Apr;104:23-33. doi: 10.1016/j.antiviral.2014.01.015. Epub 2014 Jan 30.
Influenza A viruses are a continuous threat to human health as illustrated by the 2009 H1N1 pandemic. Since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. Here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; SALPs) for their potential to inhibit influenza virus replication in vitro and in vivo. We found that particularly SALP PEP 19-2.5 shows high binding affinities for the influenza virus receptor molecule, N-Acetylneuraminic acid, leading to impaired viral attachment and cellular entry. As a result, replication of several influenza virus subtypes (H7N7, H3N2 and 2009 pandemic H1N1) was strongly reduced. Furthermore, mice co-treated with PEP 19-2.5 were protected against an otherwise 100% lethal H7N7 influenza virus infection. These findings show that SALPs exhibit antiviral activity against influenza viruses by blocking virus attachment and entry into host cells. Thus, SALPs present a new class of broad-spectrum antiviral peptides for further development for influenza virus therapy.
甲型流感病毒对人类健康构成持续威胁，2009年H1N1大流行就说明了这一点。由于流行的流感病毒株对现有药物的耐药性日益增强，迫切需要开发新型抗病毒药物。在此，我们评估了最近描述的一类新型广谱抗病毒肽（合成抗脂多糖肽；SALPs）在体外和体内抑制流感病毒复制的潜力。我们发现，特别是SALP PEP 19-2.5对流感病毒受体分子N-乙酰神经氨酸具有高结合亲和力，导致病毒附着和细胞进入受损。结果，几种流感病毒亚型（H7N7、H3N2和2009年大流行H1N1）的复制被强烈减少。此外，用PEP 19-2.5共同处理的小鼠免受了原本100%致死的H7N7流感病毒感染。这些发现表明，SALPs通过阻断病毒附着和进入宿主细胞而表现出对流感病毒的抗病毒活性。因此，SALPs是一类新型的广谱抗病毒肽，有待进一步开发用于流感病毒治疗。
