Small molecule measles virus RNA Dependent RNA Polymerase (RDRP) inhibitors.
The target market for this therapeutic agent is in the developing world where measles has been known to kill as many as one out of four people. In underdeveloped nations with high rates of malnutrition and poor healthcare, fatality rates have been as high as 28%. For immunocompromised patients (e.g., people with AIDS) with limited response to vaccination, the fatality rate due to measles infection is approximately 30%. Measles is the leading cause of blindness among African children and kills almost 1 million children in the world each year. The introduction of a therapeutic agent would be intended to complement the vaccine programs run by specific countries, not replace such programs. Moreover, in immune compromised patients that would have limited response to vaccination, this agent may be the only hope for those infected with the measles virus. These therapy may also be useful in the developed countries where measles virus vaccine rates have been declining leading to viral outbreaks.
Measles is a highly contagious viral illness that can lead to serious complications or even death. Currently, no therapies exist for the treatment of the measles virus; it is only prevented through administration of a vaccine. Despite the existence of an effective vaccine, the worldwide incidence of measles is on the rise, increasing the need for an effective treatment. The only drug currently approved for the treatment of paramyxoviruses is Ribavirin but it has limited efficacy against the measles virus while having significant adverse effects.
The small molecules that have been identified are non-nucleoside inhibitors with in vitro cellular potency in the low-nanomolar range. The lead compound also has shown no mutagenicity or hERG toxicity in vitro. They are water soluble and preliminary studies indicate they are moderately metabolically stable and orally available.
Publications
Plemper, R.K. et al. (2014). Expert Opinion Drug Discovery, 9(2), 201-214. Ndungu, J.M. et al. (2012). J Med Chem, 55(9), 4220-4230. Plemper, R.K. et al. (2009). Curr Opin Investig Drugs, 10(8), 811-820. Yoon, J.J. et al. (2009). Antimicrobial Agents and Chemotherapy, 53(9), 3860-3870. Sun, A. et al. (2008). J Med Chem, 51(13), 3731-3741. White, L.K. et al. (2007). Antimicrobial Agents and Chemotherapy, 51(7), 2293-2303.