ABSTRACT
This chapter describes the influence of structure-based approaches in the design of a class of antipicomaviral agents called capsid-binding inhibitors. Any effort at antirhinoviral therapy must attend to these three issues: serotypic diversity; exceptional safety; and viral resistance. Therefore, any structure-based approach cannot concentrate on potency alone, but must also attend to these three issues as well. The chapter introduces the target, the human rhinoviruses (HRVs), and describes their anatomy and life cycle. The human rhinoviruses are picornaviruses, a family of small, positive sense, single-stranded RNA viruses. Capsid-binding compounds were discovered long before the emergence of the HRV crystal structure. The chapter discusses the Drug structure-activity relationships, followed by a discussion of drug resistance. It also discusses clinical trials and future prospects for capsid-binding inhibitors in any antirhinoviral armamentarium. An alternative explanation for the behavior of the drug compensation mutants suggests that these mutants allow for increased conformational flexibility in the capsid.
