Introduction

Discovery of antiviral drugs has always been an opportunistic endeavor. Small molecules in general and nucleoside analogues in particular have led investigators to discover uncharacterized viral gene products that could be exploited for the purpose of antiviral chemotherapy. Great strides have also been made in understanding fundamental events in the viral replication cycle including the binding of viral glycoproteins to cellular receptors, viral regulatory proteins that control expression of viral and cellular gene expression, viral genes that affect the synthesis and packaging of the viral genome, and viral factors that subvert the host immune response (Whitley and Roizman, 2001). Many of the viral genes that contribute to these processes are known and for some of them, the precise function is understood at the molecular level. For these targets it is comparatively simple to reduce the essential function to a biochemical assay, such as a polymerase or protease assay for use in a high throughput screen in order to identify small molecule inhibitors of enzyme function (Liu and Roizman, 1993). This approach has facilitated the proactive and rational search for specific enzyme inhibitors and has led to the development of effective antiviral therapies. Although this approach is effective, it requires well-characterized targets with a defined biochemical function, and can be applied only to a very small proportion of the essential viral gene products. At present, the best targets for antiviral chemotherapy likely remain undescribed and unutilized.