Molecular wipes: application to epidemic keratoconjuctivitis

J Med Chem. 2011 Oct 13;54(19):6670-5. doi: 10.1021/jm200545m. Epub 2011 Aug 31.

Abstract

Epidemic keratoconjunctivitis (EKC) is a severe disease of the eye, caused by members of the Adenoviridae (Ad) family, with symptoms such as keratitis, conjunctivitis, pain, edema, and reduced vision that may last for months or years. There are no vaccines or antiviral drugs available to prevent or treat EKC. It was found previously that EKC-causing Ads use sialic acid as a cellular receptor and demonstrated that soluble, sialic acid-containing molecules can prevent infection. In this study, multivalent sialic acid constructs based on 10,12-pentacosadiynoic acid (PDA) have been synthesized, and these constructs are shown to be efficient inhibitors of Ad binding (IC(50) = 0.9 μM) and Ad infectivity (IC(50) = 0.7 μM). The mechanism of action is to aggregate virus particles and thereby prevent them from binding to ocular cells. Such formulations may be used for topical treatment of adenovirus-caused EKC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / drug effects*
  • Adenovirus Infections, Human / drug therapy*
  • Alkynes / chemical synthesis*
  • Alkynes / chemistry
  • Alkynes / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cells, Cultured
  • Cornea / cytology
  • Epidemics
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / virology
  • Humans
  • Keratoconjunctivitis / drug therapy*
  • Keratoconjunctivitis / virology
  • Liposomes
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology
  • Sialic Acids / chemical synthesis*
  • Sialic Acids / chemistry
  • Sialic Acids / pharmacology
  • Structure-Activity Relationship
  • Virion / drug effects

Substances

  • Alkynes
  • Antiviral Agents
  • Liposomes
  • Sialic Acids
  • Polyethylene Glycols