Abstract
We have isolated a human rhinovirus type-2 (HRV-2) mutant that is resistant to the antiviral agent chalcone Ro 09-0410 (4′-ethoxy-2′-hydroxy-4, 6′-dimethoxychalcone). This Ro 09-0410-resistant HRV-2 mutant (SR2-0410) exhibited altered biological properties when compared with the parental wild-type (wt) HRV-2. It was unstable when exposed to acid and heat in the presence of the drug, was incapable of producing plaques and produced an early cytopathic effect (CPE) at high temperatures (35°C and 37°C). Furthermore, compared with the parental wild-type, it showed a reduced ability to be neutralized by an anti-HRV-2 polyclonal serum and monoclonal antibodies. This SR2-0410 mutant demonstrated cross-resistance to other synthetic anti-rhinovirus compounds, which are also thought to bind to the viral capsid protein (VPI), such as 4′,6-dichloroflavan, 3-methoxy-6-[4-(3-methylphenyl)-I-piperazinyl] pyridazine (R 61837) and WIN 51711 (5-[7-[4-(4,5-dihydro-2-oxazolyl) phenoxyl] heptyl]-3-methyl-isoxazole). Furthermore, it was also resistant to various antiviral combinations synergistic against HRV-2. However, it was still sensitive to enviroxime [2-amino-I-(isopropyl sulphonyl)-6-benzimidazole phenyl ketone oxime], which has a different mode of action and is thought to interfere with viral RNA synthesis.