Isolation and Preliminary Characterization of Chalcone Ro 09-0410-Resistant Human Rhinovirus Type 2

Autor: Salem R. Yasin, D. A. J. Tyrrell, W. Al-Nakib
Rok vydání: 1990
Předmět:
Zdroj: Antiviral Chemistry and Chemotherapy. 1:149-154
ISSN: 2040-2066
DOI: 10.1177/095632029000100210
Popis: Summary 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'-dimethoxy­ chalcone). 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 produc­ ing plaques and produced an early cytopathic effect (OPE) at high temperatures (35°0 and 37°0). Further­ more, 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-methyl­ phenyQ- 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-benzi­ midazole phenyl ketone oxime], which has a different mode of action and is thought to interfere with viral RNA synthesis.
Databáze: OpenAIRE