Pyrimethamine inhibits rabies virus replication in vitro

Publication date: Available online 25 October 2018Source: Antiviral ResearchAuthor(s): Sophie Rogée, Florence Larrous, Dirk Jochmans, Youcef Ben-Khalifa, Johan Neyts, Hervé BourhyAbstractRabies virus transmits from animals to humans and causes encephalitis. Every year more than 15 million people receive a post exposure prophylaxis (PEP) treatment that is highly effective in the prevention of rabies disease. However, when clinical symptoms appear, for example in people who did not receive PEP, rabies is almost invariably fatal. Due to the limited access to PEP in some target populations, mostly in Asia and in Africa, rabies causes at least 59,000 deaths a year. PEP is not effective after the onset of symptoms and attempts to develop a treatment for clinical rabies have been unsuccessful. After screening a library of 385 FDA-approved drugs, we found that pyrimethamine inhibits rabies infection in vitro through the inhibition of adenosine synthesis. In addition, this compound shows a synergistic interaction with ribavirin. Unfortunately, in rabies infected-mice, pyrimethamine showed no efficacy. This can be explained by our observation that the pyrimethamine also interferes with the innate immune response.
Source: Antiviral Therapy - Category: Virology Source Type: research