Combinatorial Chemistry Online - Volume 4, Issue 11, October 2002

Abstract

Current literature highlights: Inhibitors of human rhinovirus 3C protease - The human rhinoviruses (HRVs) are members of the picornavirus family and are the single most causative agent of the common cold. Over 100 serotypes of the virus exist, so immunisation is an impractical approach to prevent the infection. Rhinoviruses contain a positive-sense strand of RNA that is translated to a large polyprotein in infected cells. This polyprotein is cleaved by viral proteases to yield mature viral enzymes and structural proteins. The 3C protease (3CP) does the majority of the proteolytic processing. Inhibition of this viral protease by a small molecule agent should stop viral replication and thus control the extent of infection. Small molecule inhibitors, such as isatins and homophthalimides, are known in the literature but these all suffer from problems such as cellular toxicity and have only modest antiviral activity. Low molecular weight non-peptidic HRV 3CP inhibitors have been synthesised (Structure-based design of a parallel synthetic array directed toward the discovery of irreversible inhibitors of human rhinovirus 3C protease, [1]).