title: An Orally Available 3-Ethoxybenzisoxazole Capsid Binder with Clinical Activity against Human Rhinovirus.
abstract: Respiratory infections caused by human rhinovirus are responsible for severe exacerbations of underlying clinical conditions such as asthma in addition to their economic cost in terms of lost working days due to illness. While several antiviral compounds for treating rhinoviral infections have been discovered, none have succeeded, to date, in reaching approval for clinical use. We have developed a potent, orally available rhinovirus inhibitor 6 that has progressed through early clinical trials. The compound shows favorable pharmacokinetic and activity profiles and has a confirmed mechanism of action through crystallographic studies of a rhinovirus-compound complex. The compound has now progressed to phase IIb clinical studies of its effect on natural rhinovirus infection in humans.
authors.affiliation: Biota Structural Biology Laboratory, St. Vincent's Institute , 9 Princes Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Feil
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hamilton
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Guy Y
authors.initials: GY
authors.lastname: Krippner
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Luttick
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Darryl B
authors.initials: DB
authors.lastname: McConnell
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Roland
authors.initials: R
authors.lastname: Nearn
authors.affiliation: Biota Structural Biology Laboratory, St. Vincent's Institute , 9 Princes Street, Fitzroy, Victoria 3065, Australia ; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , 30 Flemington Road, Parkville, Victoria 3010, Australia.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Ryan
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Stanislawski
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Tucker
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Watson
authors.affiliation: Biota Holdings Ltd. , 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia ; Biota Structural Biology Laboratory, St. Vincent's Institute , 9 Princes Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Morton
keywords: antiviral; capsid; inhibitor; rhinovirus