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

被引:7
作者
Wittwer, Kevin [1 ]
Anderson, Danielle E. [2 ]
Pfeffermann, Kristin [1 ]
Cox, Robert M. [3 ]
Wolf, Josef D. [3 ]
Santibanez, Sabine [4 ]
Mankertz, Annette [4 ]
Plesker, Roland [1 ]
Sticher, Zachary M. [5 ]
Kolkykhalov, Alexander A. [5 ]
Natchus, Michael G. [5 ]
Pfaller, Christian K. [1 ]
Plemper, Richard K. [3 ]
von Messling, Veronika [1 ,6 ]
机构
[1] Paul Ehrlich Inst, Vet Med Div, Langen, Germany
[2] Duke NUS Med Sch, Programme Emerging Infect Dis, Singapore, Singapore
[3] Georgia State Univ, Inst Biomed Sci, Atlanta, GA 30303 USA
[4] Robert Koch Inst, WHO European Reg Reference Lab Measles & Rubella, Berlin, Germany
[5] Emory Univ, Emory Inst Drug Dev, Atlanta, GA USA
[6] Fed Minist Educ & Res, Life Sci Unit, Berlin, Germany
关键词
VIRUS; VACCINATIONS; ELIMINATION; DISEASES; RECEPTOR; RUBELLA;
D O I
10.1038/s41467-021-25497-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. 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.
引用
收藏
页数:7
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