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Rhinoviral Capsid-Binding Inhibitors: Structural Basis for Understanding
Rhinoviral Biology and for Drug Design
Vincent L. Giranda
Abbott Laboratories, Abbott Park, Illinois
Guy D. Diana
ViroPharma, Inc., Malvern, Pennsylvania
I. Introduction
A cure for the common cold has been sought after so long that it has become a clicheé: “We can
_____(do something difficult) but we can't cure the common cold”. There are, unfortunately, a number
of factors that conspire to make the cure for the common cold ephemeral. In spite of these difficulties,
dramatic progress has been made in producing chemotherapies for human rhinoviruses (HRVs), which
are the major cause of the common cold in humans [1]. Although most colds are generally both mild and
self-limiting, they are responsible for both a large proportion of visits to physicians and lost work time
[2]. Billions of dollars are spent in the United States alone on symptomatic relief from this disease. The
ubiquitousness of this disease has led many people to seek a cure for many years (the discovery of the
class of HRV inhibitors described here is over 20 years old). This chapter will describe the influence of
structure-based approaches in the design of a class of antipicornaviral agents called capsid-binding
inhibitors.
Any effort to inhibit HRV replication, and thus cure many common colds, is made more difficult by
three factors. First, there are at least 102 described serotypes of HRVs, and it seems likely that there are
many more serotypes not yet described [3]. Rhinoviruses are responsible for about 40–60% of the colds
in humans [1,4]. Therefore, a chemotherapeutic agent would need to be effective
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