tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2016 May 16. pii: AAC.00709-16. [Epub ahead of print]
[h=1]Antiviral activity of Favipiravir (T-705) against a broad range of paramyxoviruses in vitro and against Human Metapneumovirus in hamsters.[/h] Jochmans D[SUP]1[/SUP], van Nieuwkoop S[SUP]2[/SUP], Smits SL[SUP]2[/SUP], Neyts J[SUP]1[/SUP], Fouchier RA[SUP]2[/SUP], van den Hoogen BG[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 EC[SUB]90[/SUB] values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with 200 mg/kg/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 limited effect on viral genome titers, would be in agreement with its proposed viral mutagenesis mode of action. 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 viral polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule would be a promising broad range antiviral drug candidate to limit the viral burden of paramyxoviruses and to be evaluated for treatment of (re-) emerging viruses such as the henipahviruses.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27185803 [PubMed - as supplied by publisher]
[h=1]Antiviral activity of Favipiravir (T-705) against a broad range of paramyxoviruses in vitro and against Human Metapneumovirus in hamsters.[/h] Jochmans D[SUP]1[/SUP], van Nieuwkoop S[SUP]2[/SUP], Smits SL[SUP]2[/SUP], Neyts J[SUP]1[/SUP], Fouchier RA[SUP]2[/SUP], van den Hoogen BG[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 EC[SUB]90[/SUB] values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with 200 mg/kg/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 limited effect on viral genome titers, would be in agreement with its proposed viral mutagenesis mode of action. 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 viral polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule would be a promising broad range antiviral drug candidate to limit the viral burden of paramyxoviruses and to be evaluated for treatment of (re-) emerging viruses such as the henipahviruses.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27185803 [PubMed - as supplied by publisher]