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An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.

Abstract：

:Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Ferrets infected with the same dose of virus that received post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic, and recovered from infection, whereas control animals succumbed to the disease. Animals that recovered also mounted a robust immune response and were protected against rechallenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found to be attenuated and transmission-impaired compared to the genetic parent virus. These findings may pioneer a path toward an effective morbillivirus therapy that could aid measles eradication by synergizing with vaccination to close gaps in herd immunity due to vaccine refusal.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Krumm SA,Yan D,Hovingh ES,Evers TJ,Enkirch T,Reddy GP,Sun A,Saindane MT,Arrendale RF,Painter G,Liotta DC,Natchus MG,von Messling V,Plemper RK

doi

10.1126/scitranslmed.3008517

subject

Has Abstract

pub_date

2014-04-16 00:00:00

pages

232ra52

issue

232

eissn

1946-6234

issn

1946-6242

pii

6/232/232ra52

journal_volume

6

pub_type

杂志文章

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