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

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 infec...

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Bibliographic Details
Published in:	Nature communications Vol. 12; no. 1; p. 5233
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 02-09-2021 Nature Publishing Group Nature Portfolio
Subjects:	631/326/596/1296 631/326/596/1631 692/308/2778 692/699/255/2514 Animals Bioavailability Cough Drug Evaluation, Preclinical Enzyme Inhibitors - pharmacokinetics Enzyme Inhibitors - therapeutic use Epidemics Fever Health services Humanities and Social Sciences Immune Tolerance - drug effects Immunity, Humoral - drug effects Immunosuppression Infections Inhibitors Lymphocytes Measles Measles - prevention & control Measles virus - drug effects Monkeys Monkeys & apes Morpholines - pharmacokinetics Morpholines - therapeutic use multidisciplinary Outbreaks Pathogens Piperidines - pharmacokinetics Piperidines - therapeutic use Prophylaxis Pyrazoles - pharmacokinetics Pyrazoles - therapeutic use RNA-Dependent RNA Polymerase - antagonists & inhibitors Saimiri Science Science (multidisciplinary) Squirrels Vaccines Virus Replication - drug effects Virus Shedding - drug effects Viruses
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Summary:	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. Measles virus is highly contagious and outbreaks occur worldwide. Here the authors show that the orally bioavailable small-molecule polymerase inhibitor ERDRP-0519 prevents measles disease in squirrel monkeys and reduces virus shedding.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-021-25497-4