Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany.
Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany.
Antiviral Res. 2020 May;177:104779. doi: 10.1016/j.antiviral.2020.104779. Epub 2020 Mar 21.
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.
人巨细胞病毒（HCMV）感染可导致新生儿和免疫功能低下患者发生严重疾病。由于治疗选择有限，因此需要新的治疗方法。防御素是一种阳离子肽，由多种人体组织产生，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，产生具有增强活性的较小片段。综上所述，这使我们假设防御素衍生肽是天然的人类病毒感染抑制剂，具有低毒性。我们筛选了几种人防御素 HNP4 和 HD5 衍生肽，发现 HD5（1-9）在高浓度下无毒性但具有抗病毒活性。HD5（1-9）抑制 HCMV 细胞附着，从而抑制进入，并对原发性和多耐药性 HCMV 分离株均具有活性。此外，鉴定出半胱氨酸和精氨酸残基介导 HD5（1-9）的抗病毒活性。总之，防御素衍生肽，特别是 HD5（1-9），有资格作为进一步开发的有前途的候选物，作为新型 HCMV 进入抑制剂。
