Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding

Wittwer, Kevin; Anderson, Danielle E.; Pfeffermann, Kristin; Cox, Robert M.; Wolf, Josef D.; Santibanez, Sabine; Mankertz, Annette; Plesker, Roland; Sticher, Zachary M.; Kolkykhalov, Alexander A.; Natchus, Michael G.; Pfaller, Christian K.; Plemper, Richard K.; von Messling, Veronika

Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the availability of effective vaccine prophylaxis, measles outbreaks continue to occur worldwide. We demonstrate that prophylactic and post-exposure therapeutic treatment with an orally bioavailable small-molecule polymerase inhibitor, ERDRP-0519, prevents measles disease in squirrel monkeys (Saimiri sciureus). Treatment initiation at the onset of clinical signs reduced virus shedding, which may support outbreak control. Results show that this clinical candidate has the potential to alleviate clinical measles and augment measles virus eradication.