Favipiravir (T-705), a novel viral RNA polymerase inhibitor.

Abstract

Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral drug that selectively inhibits the RNA-dependent RNA polymerase of influenza virus. It is phosphoribosylated by cellular enzymes to its active form, favipiravir-ribofuranosyl-5'-triphosphate (RTP). Its antiviral effect is attenuated by the addition of purine nucleic acids, indicating the viral RNA polymerase mistakenly recognizes favipiravir-RTP as a purine nucleotide. Favipiravir is active against a broad range of influenza viruses, including A(H1N1)pdm09, A(H5N1) and the recently emerged A(H7N9) avian virus. It also inhibits influenza strains resistant to current antiviral drugs, and shows a synergistic effect in combination with oseltamivir, thereby expanding influenza treatment options. A Phase III clinical evaluation of favipiravir for influenza therapy has been completed in Japan and two Phase II studies have been completed in the United States. In addition to its anti-influenza activity, favipiravir blocks the replication of many other RNA viruses, including arenaviruses (Junin, Machupo and Pichinde); phleboviruses (Rift Valley fever, sandfly fever and Punta Toro); hantaviruses (Maporal, Dobrava, and Prospect Hill); flaviviruses (yellow fever and West Nile); enteroviruses (polio- and rhinoviruses); an alphavirus, Western equine encephalitis virus; a paramyxovirus, respiratory syncytial virus; and noroviruses. With its unique mechanism of action and broad range of antiviral activity, favipiravir is a promising drug candidate for influenza and many other RNA viral diseases for which there are no approved therapies.

• Authors: Yousuke Furuta, Brian B Gowen, Kazumi Takahashi, Kimiyasu Shiraki, Donald F Smee, Dale L Barnard
• Journal: Antiviral research (Antiviral Res) Vol. 100 Issue 2 Pg. 446-54 (Nov 2013) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 24084488 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Amides
• Antiviral Agents
• Enzyme Inhibitors
• Pyrazines
• DNA-Directed RNA Polymerases
• favipiravir

Topics

• Amides (isolation & purification, pharmacology, therapeutic use)
• Antiviral Agents (isolation & purification, pharmacology, therapeutic use)
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• DNA-Directed RNA Polymerases (antagonists & inhibitors)
• Enzyme Inhibitors (isolation & purification, pharmacology, therapeutic use)
• Humans
• Influenza, Human (drug therapy)
• Japan
• Pyrazines (isolation & purification, pharmacology, therapeutic use)
• RNA Viruses (drug effects)
• United States