Potent inhibition of enterovirus D68 and human rhinoviruses by dipeptidyl aldehydes and α-ketoamides

Yunjeong Kim, Anushka C.Galasiti Kankanamalage, Vishnu C. Damalanka, Pathum M. Weerawarna, William C. Groutas, Kyeong Ok Chang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Enterovirus D68 (EV-D68) is an emerging pathogen responsible for mild to severe respiratory infections that occur mostly in infants, children and teenagers. EV-D68, one of more than 100 non-polio enteroviruses, is acid-labile and biologically similar to human rhinoviruses (HRV) (originally classified as HRV87). However, there is no approved preventive or therapeutic measure against EV-D68, HRV, or other enteroviruses. In this study, we evaluated the antiviral activity of series of dipeptidyl compounds against EV-D68 and HRV strains, and demonstrated that several peptidyl aldehyde and α-ketoamide peptidyl compounds are potent inhibitors of EV-D68 and HRV strains with high in-vitro therapeutic indices (>1000). One of the α-ketoamide compounds is shown to have favorable pharmacokinetics profiles, including a favorable oral bioavailability in rats. Recent successful development of α-ketoamide protease inhibitors against hepatitis C virus suggests these compounds may have a high potential for further optimization and development against emerging EV-D68, as well as HRV.

Original languageEnglish
Pages (from-to)84-91
Number of pages8
JournalAntiviral Research
Volume125
DOIs
StatePublished - Jan 1 2016

Keywords

  • Aldehyde and α-ketoamide peptidyl compounds
  • Antivirals
  • Enterovirus D68
  • Human rhinovirus

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