Rabies remains the deadliest viral disease known. This gruesome viral disease of the brain continues to kill more than 50,000 humans worldwide each year. An effective vaccine exists, but its high cost (more than $1,000 per series) is prohibitive and it is only effective if given prior to onset of clinical symptoms. Once clinical rabies is manifest, the disease is still effectively a death sentence.
Prosetta has used its proprietary cell free protein synthesis and assembly approach in phenotypic screens to identify and develop small molecules that block rabies infection. Prosetta’s initial rabies compound was potent against infectious virus in cell culture, caused a 100-fold drop in viral titer in mouse brain, and, when given once daily, significantly extended the lives of animals inoculated with a lethal dose of rabies virus.
This compound was also the first of several Prosetta rabies compounds to display an extremely useful property in addition to its ability to halt the spread of viral infection. Rabies-infected cells treated with Prosetta compounds generate non-infectious viral particles that lead to the production of extremely high titers of broadly neutralizing rabies antibodies in animals. Thus, Prosetta molecules have the additional potential application of generating non-infectious viral particles as ideal immunogens for difficult vaccine challenges.
Prosetta has steadily improved its rabies compounds, with the current generation lead compound at least 50 fold more potent and 10 fold more bioavailable than any previous compound. We are ready to proceed to animal efficacy trials as soon as resources are identified to support this work.