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T-705 (favipiravir) activity against lethal H5N1 influenza A viruses
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T-705 (favipiravir) activity against lethal H5N1 influenza A viruses
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Journal Article
T-705 (favipiravir) activity against lethal H5N1 influenza A viruses
2010
Overview
The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivir-resistant H5N1 viruses, rendering the oseltamivir stockpile obsolete. Therefore, there is a need for unique and effective antivirals to combat H5N1 influenza viruses. The investigational drug T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has antiviral activity against seasonal influenza viruses and a mouse-adapted H5N1 influenza virus derived from a benign duck virus. However, its efficacy against highly pathogenic H5N1 viruses, which are substantially more virulent, remains unclear. Here, we demonstrate that T-705 effectively protects mice from lethal infection with oseltamivir-sensitive or -resistant highly pathogenic H5N1 viruses. Furthermore, our biochemical analysis suggests that T-705 ribofuranosyl triphosphate, an active form of T-705, acts like purines or purine nucleosides in human cells and does not inhibit human DNA synthesis. We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Animals
/ Antiviral Agents - pharmacology
/ Cells
/ Child
/ DNA
/ DNA Replication - drug effects
/ DNA-Directed DNA Polymerase - drug effects
/ DNA-Directed DNA Polymerase - metabolism
/ Dogs
/ Dosage
/ drugs
/ ducks
/ H5N1 subtype influenza A virus
/ Humans
/ Influenza A Virus, H5N1 Subtype - drug effects
/ Influenza, Human - drug therapy
/ Influenza, Human - mortality
/ Kidney
/ Kinetics
/ Lungs
/ Mice
/ patients
/ purines
/ Rodents
/ Viruses
/ Wildfowl
