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Peste des petits ruminants (PPR) is a virus disease of sheep and goats in West Africa. When first described, the virus was considered a variant of rinderpest virus. The biological and physicochemical characteristics of the virus indicate that it is closely related to measles, rinderpest and canine distemper viruses. These three viruses form the genus Morbillivirus of the Paramyxoviridae. PPR virus is sufficiently distinct from these 3 viruses to justify considering it as the fourth member of the Morbillivirus genus.

In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C., Leong, M. A., and Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.

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