Research ArticleInfectious diseases

An Orally Available, Small-Molecule Polymerase Inhibitor Shows Efficacy Against a Lethal Morbillivirus Infection in a Large Animal Model

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Science Translational Medicine  16 Apr 2014:
Vol. 6, Issue 232, pp. 232ra52
DOI: 10.1126/scitranslmed.3008517

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A Boon for Measles Eradication

Measles virus causes about 150,000 deaths per year globally despite the existence of an effective vaccine. Insufficient vaccination coverage and vaccine refusal cause gaps in population immunity that challenge current measles virus eradication goals. In their new work, Krumm et al. explore whether an antiviral therapeutic blocking the measles virus RNA polymerase can aid in solving this problem by suppressing measles-like disease. The authors show that the drug efficiently inhibits the RNA polymerase of canine distemper virus (CDV), which is closely related to the measles virus and causes lethal, measles-like disease in ferrets. They demonstrated that prophylactic treatment of CDV-infected ferrets by mouth reduced viral load and prolonged survival. When treatment was initiated 3 days after infection, disease was completely suppressed. All of the animals survived the infection and developed immunity against the virus, which protected against later challenge with a lethal virus dose. Next, the authors generated drug-resistant CDV strains and demonstrated that resistant viruses caused milder disease than did the parent strain and were transmitted less efficiently between animals. These results suggest that this drug may be useful in the future for preemptive treatment of unprotected human contacts of measles cases.

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