Human cytomegalovirus (HCMV) infection causes severe illness in newborns and immunocompromised patients. Since treatment options are limited there is an unmet need for new therapeutic approaches. Defensins are cationic peptides, produced by various human tissues, which serve as antimicrobial effectors of the immune system. Furthermore, some defensins are proteolytically cleaved, resulting in the generation of smaller fragments with increased activity. Together, this led us to hypothesize that defensin-derived peptides are natural human inhibitors of virus infection with low toxicity. We screened several human defensin HNP4- and HD5-derived peptides and found HD5(1-9) to be antiviral without toxicity at high concentrations. HD5(1-9) inhibited HCMV cellular attachment and thereby entry and was active against primary as well as a multiresistant HCMV isolate. Moreover, cysteine and arginine residues were identified to mediate the antiviral activity of HD5(1-9). Altogether, defensin-derived peptides, in particular HD5(1-9), qualify as promising candidates for further development as a novel class of HCMV entry inhibitors.

中文翻译：

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人α-防御素衍生肽HD5（1-9）抑制人巨细胞病毒的细胞附着和进入。

人巨细胞病毒（HCMV）感染会在新生儿和免疫受损的患者中引起严重疾病。由于治疗选择有限，因此对新治疗方法的需求未得到满足。防御素是由各种人体组织产生的阳离子肽，可作为免疫系统的抗菌效应物。此外，一些防御素被蛋白水解切割，导致产生具有增加的活性的较小片段。总之，这使我们假设防御素衍生肽是病毒感染的天然人类抑制剂，毒性低。我们筛选了几种人类防御素HNP4和HD5衍生的肽，发现HD5（1-9）具有抗病毒性，在高浓度下无毒性。HD5（1-9）抑制HCMV细胞附着并因此进入，并具有抗原发性和多重耐药性HCMV分离物的活性。此外，鉴定出半胱氨酸和精氨酸残基可介导HD5（1-9）的抗病毒活性。总而言之，防御素衍生的肽，特别是HD5（1-9），有资格作为新型HCMV进入抑制剂进一步开发的有希望的候选者。