Antiviral Activity of Favipiravir (T-705) against a Broad Range of Paramyxoviruses In Vitro and against Human Metapneumovirus in Hamsters
| Autor: | Johan Neyts, S van Nieuwkoop, Ron A. M. Fouchier, Dirk Jochmans, Saskia L. Smits, B G van den Hoogen |
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| Přispěvatelé: | Virology |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class viruses Favipiravir Antibodies Viral Virus Replication Antiviral Agents Virus Measles virus 03 medical and health sciences Human metapneumovirus Cricetinae Chlorocebus aethiops medicine Animals Humans Pharmacology (medical) Lung Vero Cells Pharmacology Paramyxoviridae Infections Mesocricetus biology virus diseases RNA virus biology.organism_classification Amides Virology Respiratory Syncytial Viruses HEK293 Cells 030104 developmental biology Infectious Diseases Viral replication Pyrazines Metapneumovirus Antiviral drug Viral load |
| Zdroj: | Antimicrobial Agents & Chemotherapy, 60(8), 4620-4629. American Society for Microbiology |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | The clinical impact of infections with respiratory viruses belonging to the family Paramyxoviridae argues for the development of antiviral therapies with broad-spectrum activity. Favipiravir (T-705) has demonstrated potent antiviral activity against multiple RNA virus families and is presently in clinical evaluation for the treatment of influenza. Here we demonstrate in vitro activity of T-705 against the paramyxoviruses human metapneumovirus (HMPV), respiratory syncytial virus, human parainfluenza virus, measles virus, Newcastle disease virus, and avian metapneumovirus. In addition, we demonstrate activity against HMPV in hamsters. T-705 treatment inhibited replication of all paramyxoviruses tested in vitro , with 90% effective concentration (EC 90 ) values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with T-705 at 200 mg/kg of body weight/day resulted in 100% protection from infection of the lungs. In all treated and challenged animals, viral RNA remained detectable in the respiratory tract. The observation that T-705 treatment had a significant effect on infectious viral titers, with a limited effect on viral genome titers, is in agreement with its proposed mode of action of viral mutagenesis. However, next-generation sequencing of viral genomes isolated from treated and challenged hamsters did not reveal (hyper)mutation. Polymerase activity assays revealed a specific effect of T-705 on the activity of the HMPV polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule is a promising broad-range antiviral drug candidate for limiting the viral burden of paramyxoviruses and for evaluation for treatment of infections with (re)emerging viruses, such as the henipaviruses. |
| Databáze: | OpenAIRE |
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