Identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections

  • ACS Med Chem Lett. 2013 May 8;4(7):585-9. doi: 10.1021/ml400095m.
Angus M MacLeod  1 ,  Dale R Mitchell  1 ,  Nicholas J Palmer  1 ,  Hervé Van de Poël  1 ,  Katja Conrath  2 ,  Martin Andrews  2 ,  Pieter Leyssen  3 ,  Johan Neyts  3
Affiliations
  • 1. Medicinal Chemistry Department, BioFocus , Chesterford Research Park, Cambridge, CB10 1XL, U.K.
  • 2. Galapagos NV , Generaal de Wittelaan, 2800 Mechelen, Belgium.
  • 3. Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven , Leuven, Belgium.
PMID: 24900715 DOI: 10.1021/ml400095m
Abstract

Rhinovirus (genus Enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. Other members of the genus can cause life-threatening acute neurological infections. There is currently no Antiviral drug approved for the treatment of such infections. We have identified a series of potent, broad-spectrum Antiviral compounds that inhibit the replication of the human rhinovirus, Coxsackie virus, poliovirus, and enterovirus-71. The mechanism of action of the compounds has been established as inhibition of a lipid kinase, PI4KIIIβ. Inhibition of hepatitis C replication in a replicon assay correlated with Enterovirus inhibition.

Keywords
HCV; PI4KIIIβ; antiviral; enterovirus; inhibitor.