Antiviral Activity of a Cyclic Pro-Pro- β3-HoPhe-Phe Tetrapeptide against HSV-1 and HAdV-5

Molecules. 2022 May 31;27(11):3552. doi: 10.3390/molecules27113552.

Abstract

The core of Cyclolinopeptide A (CLA, cyclo(LIILVPPFF)), responsible for its high immunosuppressive activity, contains a Pro-Pro-Phe-Phe sequence. A newly synthesized cyclic tetrapeptide, cyclo(Pro-Pro-β3-HoPhe-Phe) (denoted as 4B8M) bearing the active sequence of CLA, was recently shown to exhibit a wide array of anti-inflammatory properties in mouse models. In this investigation, we demonstrate that the peptide significantly inhibits the replication of human adenovirus C serotype 5 (HAdV-5) and Herpes simplex virus type-1 (HSV-1) in epithelial lung cell line A-549, applying Cidofovir and Acyclovir as reference drugs. Based on a previously established mechanism of its action, we propose that the peptide may inhibit virus replication by the induction of PGE2 acting via EP2/EP4 receptors in epithelial cells. In summary, we reveal a new, antiviral property of this anti-inflammatory peptide.

Keywords: A-549; HAdV-5; HSV-1; antiviral activity; cyclic tetrapeptide cyclo(Pro-Pro-β3-HoPhe-Phe).

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Dipeptides
  • Herpesvirus 1, Human*
  • Immunosuppressive Agents / pharmacology
  • Mice
  • Peptides
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology

Substances

  • Antiviral Agents
  • Dipeptides
  • Immunosuppressive Agents
  • Peptides
  • Peptides, Cyclic
  • prolyl-proline