title: Anti-rhinovirus activity of 3-methylthio-5-aryl-4-isothiazolecarbonitrile derivatives.
abstract: A series of 3-methylthio-5-aryl-4-isothiazolecarbonitriles has been evaluated as anti rhinovirus agents against a panel of 17 representative human rhinovirus (HRV) serotypes, belonging to both A and B groups. No anti rhinovirus activity was detected for 3-methylthio-5-phenyl-4-isothiazolecarbonitrile (IS-2). Isothiazole derivatives with bulky substituents (O-Bn or O-But groups) on the para position of the phenyl ring were the most effective compounds of this series. In fact, a reduction in virus-induced cytopathogenicity was demonstrated for the O-Bn substituted IS-50 compound against the majority (88%) of the rhinoviruses tested, whereas the compound with an O-Ts group (IS-44) was found to be a specific inhibitor of group B serotypes, exhibiting the lowest IC(50) against HRVs type 2, 85 and 89. Our studies on the mechanism of action of IS-44 demonstrated that it prevents the thermal inactivation of HRV 2 infectivity, probably due to a conformational shift in the viral capsid and a decrease in affinity for the cellular receptor, resulting in an inhibition of attachment of the virions.
authors.affiliation: Department of Microbiological and Gynaecological Sciences, University of Catania, Via Androne 81, 95124, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Garozzo
authors.forename: C C
authors.initials: CC
authors.lastname: Cutrì
authors.forename: A
authors.initials: A
authors.lastname: Castro
authors.forename: G
authors.initials: G
authors.lastname: Tempera
authors.forename: F
authors.initials: F
authors.lastname: Guerrera
authors.forename: M C
authors.initials: MC
authors.lastname: Sarvà
authors.forename: E
authors.initials: E
authors.lastname: Geremia
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D012229:Rhinovirus / Q000187:drug effects*; D013696:Temperature; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013997:Time Factors; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D013844:Thiazoles