R 61 837, a new antirhinovirus compound, was able to protect several susceptible rhinoviruses against inactivation by mild acidification or heat. This observation strengthens the hypothesis that the drug exerts antiviral activity by a direct interaction with the viral protein capsid to stabilize the particle. However, the minimal concentrations necessary to inhibit either acetate or citrate or heat inactivation were different for each of five tested serotypes and we therefore conclude that stabilization and inhibition of replication are not causally linked but parallel events, both independently resulting from the binding of the drug to the viral capsid. Studies using drug resistant mutants of HRV 51 and HRV 9 confirmed this lack of quantitative correlation. The mutants were also shown to be cross resistant to a panel of seven different reference antirhinoviral drugs including SDS, WIN 51711, chalcone, dichloroflavan and MDL 20,610. This indicates that all these compounds bind to the same site corresponding to the hydrophobic pocket within the viral protein VP 1 β-barrel structure of HRV 14.
