title: Identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections.
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.
authors.affiliation: Medicinal Chemistry Department, BioFocus , Chesterford Research Park, Cambridge, CB10 1XL, U.K.
authors.forename: Angus M
authors.initials: AM
authors.lastname: MacLeod
authors.affiliation: Medicinal Chemistry Department, BioFocus , Chesterford Research Park, Cambridge, CB10 1XL, U.K.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Mitchell
authors.affiliation: Medicinal Chemistry Department, BioFocus , Chesterford Research Park, Cambridge, CB10 1XL, U.K.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Palmer
authors.affiliation: Medicinal Chemistry Department, BioFocus , Chesterford Research Park, Cambridge, CB10 1XL, U.K.
authors.forename: Hervé
authors.initials: H
authors.lastname: Van de Poël
authors.affiliation: Galapagos NV , Generaal de Wittelaan, 2800 Mechelen, Belgium.
authors.forename: Katja
authors.initials: K
authors.lastname: Conrath
authors.affiliation: Galapagos NV , Generaal de Wittelaan, 2800 Mechelen, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Andrews
authors.affiliation: Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven , Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven , Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
keywords: HCV; PI4KIIIβ; antiviral; enterovirus; inhibitor