Potency of a small molecule that targets the molluscum contagiosum virus processivity factor increases when conjugated to a tripeptide

Antiviral Res. 2024 Jun:226:105899. doi: 10.1016/j.antiviral.2024.105899. Epub 2024 May 3.

Abstract

We recently developed compound FC-7269 for targeting the Molluscum contagiosum virus processivity factor (mD4) and demonstrated its ability to inhibit viral processive DNA synthesis in vitro and cellular infection of an mD4-dependent virus (Antiviral Res 211, 2023,105520). However, despite a thorough medicinal chemistry campaign we were unable to generate a potent second analog as a requisite for drug development. We overcame this impasse, by conjugating a short hydrophobic trivaline peptide to FC-7269 to produce FC-TriVal-7269 which significantly increased antiviral potency and reduced cellular toxicity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antiviral Agents* / chemical synthesis
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Cell Line
  • Humans
  • Molluscum Contagiosum / drug therapy
  • Molluscum contagiosum virus* / drug effects
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Virus Replication / drug effects