W0204

Structure of WIN52035-Dependent Human Rhinovirus 16 Mutant. Sukyeong Lee, Wensheng Wang, Carol M Bator and Michael G. Rossmann, Department of Biological Sciences, Purdue University, West Lafayette, IN 47907

Rhinoviruses belong to the picornavirus family and are small, icosahedral, non-enveloped viruses containing one positive RNA strand. Human rhinoviruses (HRV) are the major causative agents of the common cold. HRV16 belongs to the major receptor group of rhinoviruses, for which the cellular receptor is intercellular adhesion molecule-1 (ICAM-1). Many rhinoviruses have hydrophobic pockets, below their receptor binding sites, occupied by a fatty acid-like molecule or so-called `pocket factor'. Antiviral compounds have been shown to bind into this hydrophobic pocket, replacing the pocket factor. The binding of antiviral compounds blocks receptor attachment and/or uncoating of the virus.

The structure has been determined of an HRV16 drug dependent mutant (V1210A) that forms plaques in the presence but not in the absence of the selecting antiviral drug, WIN52035. The mutation site is located in the protomer-protomer interface. There are major differences in structure between wild type HRV16 (with pocket factor) and the mutant virus (with antiviral drug). These differences are far greater than those observed between wild type HRV16 and wild type HRV16 when bound with an antiviral drug. The structural changes of the mutant virus and their relation to viral stability are now being analysed.