The human α-defensin-derived peptide HD5(1–9) inhibits cellular attachment and entry of human cytomegalovirus

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2020
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Böffert, Rebecca
Businger, Ramona
Preiß, Hannes
Ehmann, Dirk
Truffault, Vincent
Simon, Claudia
Ruetalo, Natalia
Hamprecht, Klaus
Schindler, Michael
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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.

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ISO 690BÖFFERT, Rebecca, Ramona BUSINGER, Hannes PREISS, Dirk EHMANN, Vincent TRUFFAULT, Claudia SIMON, Natalia RUETALO, Klaus HAMPRECHT, Patrick MÜLLER, Michael SCHINDLER, 2020. The human α-defensin-derived peptide HD5(1–9) inhibits cellular attachment and entry of human cytomegalovirus. In: Antiviral Research. Elsevier. 2020, 177, 104779. ISSN 0166-3542. eISSN 1872-9096. Available under: doi: 10.1016/j.antiviral.2020.104779
BibTex
@article{Boffert2020human-56289,
  year={2020},
  doi={10.1016/j.antiviral.2020.104779},
  title={The human α-defensin-derived peptide HD5(1–9) inhibits cellular attachment and entry of human cytomegalovirus},
  volume={177},
  issn={0166-3542},
  journal={Antiviral Research},
  author={Böffert, Rebecca and Businger, Ramona and Preiß, Hannes and Ehmann, Dirk and Truffault, Vincent and Simon, Claudia and Ruetalo, Natalia and Hamprecht, Klaus and Müller, Patrick and Schindler, Michael},
  note={Article Number: 104779}
}
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