Il morbillo è una delle più comuni e pericolose infezioni virali dell’infanzia; nonostante l’esistenza di un vaccino efficace si calcolano in miliardi di euro ed in milioni di persone con danni permanenti i problemi da esso provocati; una nuova molecola che riesce ad inibire per la prima volta la RNA polimerasi del virus del morbillo in un modello animale promette di essere un passo decisivo verso la sua eradicazione dal pianeta.
Sci Transl Med 16 April 2014:
Vol. 6, Issue 232, p. 232ra52
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3008517
• Research Article
IS. A. Krumm, D. Yan, E. S. Hovingh, T. J. Evers, T. Enkirch, G. P. Reddy, A. Sun, M. T. Saindane, R. F. Arrendale, G. Painter, D. C. Liotta, M. G. Natchus, V. von Messling, R. K. Plemper, An Orally Available, Small-Molecule Polymerase Inhibitor Shows Efficacy Against a Lethal Morbillivirus Infection in a Large Animal Model. Sci. Transl. Med. 6, 232ra52 (2014).
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.