Candidate anti-herpesviral drugs; mechanisms of action and resistance

Abstract

Research into the molecular biology of herpes replication in recent years has revealed novel targets for drug development (Fig. 68.1). The characterization and functional assay of these targets have been facilitated by advancements in gene expression, protein purification, proteonomics, bioinformatics, and efficient robotic screening technologies. The pipeline for new herpes drugs has been expanding as drug candidates have evolved more rapidly due to improvements in chemical synthesis (i.e., combinatorial and parallel synthesis methods), and with aids for drug design (X-ray crystallography, in silico computer modeling tools, as well as chemoinformatics). Many new herpes inhibitors have been reported, and most of these possess novel modes of actions. Several have entered clinical evaluation, with some later discontinued because of safety issues. This chapter will describe promising drug candidates in early development that appear to act at individual steps of the viral replication cycle, and focus on those that have the most potential for success (Table 68.1).