Abstract
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.
Highlights
Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route
During an incubation period of ~10–14 days, infected cells home to mediastinal lymph nodes, where the virus infects resident SLAM/CD150+T- and B-cells[1,2]. This event results in peripheral blood mononuclear cell (PBMC)associated viremia and is followed by viral spread to epithelial cells, which coincides with the onset of clinical signs including fever, conjunctivitis, and the measles-typical rash[2]
Efficacy of ERDRP-0519 against MeV at concentrations achieved in vivo
Summary
Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. During an incubation period of ~10–14 days, infected cells home to mediastinal lymph nodes, where the virus infects resident SLAM/CD150+T- and B-cells[1,2] This event results in peripheral blood mononuclear cell (PBMC)associated viremia and is followed by viral spread to epithelial cells, which coincides with the onset of clinical signs including fever, conjunctivitis, and the measles-typical rash[2]. Since 2017, and before COVID-19, lapsed vaccination coverage has resulted in measles reappearing in geographic regions that had previously been declared measlesfree These challenges create an urgent need for the development of effective pharmacological countermeasures that can consolidate progress towards global measles control and support vaccination-based eradication efforts[11]. To assess the clinical potential of the compound, we evaluated in this study the oral efficacy against a clinical MeV isolate in non-human primates, which develop human measles-like disease
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