Favipiravir

Favipiravir
Names
IUPAC name
5-Fluoro-2-oxo-1H-pyrazine-3-carboxamide
Other names
T-705
Identifiers
259793-96-9
ChEMBL ChEMBL221722
ChemSpider 431002
Jmol 3D model Interactive image
PubChem 492405
Properties
C5H4FN3O2
Molar mass 157.10 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Favipiravir, also known as T-705 or Avigan, is an experimental antiviral drug being developed by Toyama Chemical of Japan with activity against many RNA viruses. Like some other experimental antiviral drugs (T-1105 and T-1106), it is a pyrazinecarboxamide derivative. Favipiravir is active against influenza viruses, West Nile virus, yellow fever virus, foot-and-mouth disease virus as well as other flaviviruses, arenaviruses, bunyaviruses and alphaviruses.[1] Activity against enteroviruses [2] and Rift Valley fever virus has also been demonstrated.[3]

The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase.[4] Other research suggests that favipiravir induces lethal RNA transversion mutations, producing a nonviable viral phenotype.[5] Favipiravir is a prodrug and is metabolized to its active form, favirpiravir-RTP, following digestion.[6] Human hypoxanthine guanine phosphoribosyltransferase (HGPRT) is believed to play a key role in this activation process.[7] Favipiravir does not inhibit RNA or DNA synthesis in mammalian cells and is not toxic to them.[1]

In 2014, favipiravir was approved in Japan for stockpiling against influenza pandemics.[8]

Ebola virus disease

The drug appears to be effective in a mouse model of Ebola virus disease, but its efficacy against human Ebola infection is unproved.[9][10][11] During the 2014 West Africa Ebola virus outbreak, it was reported that a French nurse who contracted Ebola while volunteering for MSF in Liberia recovered after receiving a course of favipiravir.[12] A clinical trial investigating the use of favipiravir against Ebola virus disease was started in Guéckédou, Guinea, during December 2014.[13] Preliminary results showed a decrease in mortality rate in patients with low-to-moderate levels of Ebola virus in the blood, but no effect on patients with high levels of the virus, a group at a higher risk of death.[14] The trial design has been criticised by Scott Hammer and others for using only historical controls.[15] The results of this clinical trial have been presented in February at the annual Conference on Retroviruses and Opportunistic Infections (CROI) 2016 by Daouda Sissoko[16] and published on March 1, 2016 in PLOS Medicine.[17]

See also

References

  1. 1 2 Furuta, Y.; Takahashi, K.; Shiraki, K.; Sakamoto, K.; Smee, D. F.; Barnard, D. L.; Gowen, B. B.; Julander, J. G.; Morrey, J. D. (2009). "T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections". Antiviral Research 82 (3): 95–102. doi:10.1016/j.antiviral.2009.02.198. PMID 19428599.
  2. ↑ Furuta, Y.; Gowen, B. B.; Takahashi, K.; Shiraki, K.; Smee, D. F.; Barnard, D. L. (2013). "Favipiravir (T-705), a novel viral RNA polymerase inhibitor". Antiviral Research 100 (2): 446. doi:10.1016/j.antiviral.2013.09.015. PMID 24084488.
  3. ↑ Caroline AL, Powell DS, Bethel LM, Oury TD, Reed DS, et al. (2014) Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever. PLoS Neglected Tropical Diseases 8(4): e2790. doi:10.1371/journal.pntd.0002790
  4. ↑ Jin, Z; Smith, L. K.; Rajwanshi, V. K.; Kim, B; Deval, J (2013). "The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5'-triphosphate towards influenza a virus polymerase". PLoS ONE 8 (7): e68347. doi:10.1371/journal.pone.0068347. PMC 3707847. PMID 23874596.
  5. ↑ Baranovich, Tatiana; Wong, Sook-San; Armstrong, Jianling; Marjuki, Henju; Webby, Richard J.; Webster, Robert G.; Govorkova, Elena A. (2013-04-01). "T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro". Journal of Virology 87 (7): 3741–3751. doi:10.1128/JVI.02346-12. ISSN 1098-5514. PMC 3624194. PMID 23325689.
  6. ↑ Smee, Donald F.; Hurst, Brett L.; Egawa, Hiroyuki; Takahashi, Kazumi; Kadota, Takumi; Furuta, Yousuke (2009-07-29). "Intracellular metabolism of favipiravir (T-705) in uninfected and influenza A (H5N1) virus-infected cells". Journal of Antimicrobial Chemotherapy: dkp274. doi:10.1093/jac/dkp274. ISSN 0305-7453. PMC 2740635. PMID 19643775.
  7. ↑ Naesens, Lieve; Guddat, Luke W.; Keough, Dianne T.; van Kuilenburg, André B. P.; Meijer, Judith; Vande Voorde, Johan; Balzarini, Jan (2013-10-01). "Role of human hypoxanthine guanine phosphoribosyltransferase in activation of the antiviral agent T-705 (favipiravir)". Molecular Pharmacology 84 (4): 615–629. doi:10.1124/mol.113.087247. ISSN 1521-0111. PMID 23907213.
  8. ↑ Koons, Cynthia (7 August 2014). "Ebola Drug From Japan May Emerge Among Key Candidates". Bloomberg.com.
  9. ↑ Gatherer D (2014). "The 2014 Ebola virus disease outbreak in West Africa". J. Gen. Virol. 95 (Pt 8): 1619–1624. doi:10.1099/vir.0.067199-0. PMID 24795448.
  10. ↑ Oestereich, L.; Lüdtke, A.; Wurr, S.; Rieger, T.; Muñoz-Fontela, C.; Günther, S. (2014). "Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model". Antiviral Research 105: 17–21. doi:10.1016/j.antiviral.2014.02.014. PMID 24583123.
  11. ↑ Smither, S. J.; Eastaugh, L. S.; Steward, J. A.; Nelson, M; Lenk, R. P.; Lever, M. S. (2014). "Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model". Antiviral Research 104: 153–5. doi:10.1016/j.antiviral.2014.01.012. PMID 24462697.
  12. ↑ http://www.msn.com/en-gb/news/world/french-nurse-cured-of-ebola-contracted-in-liberia/ar-BB7r1UJ
  13. ↑ "Guinea: Clinical Trial for Potential Ebola Treatment Started in MSF Clinic in Guinea". AllAfrica - All the Time. Retrieved 28 December 2014.
  14. ↑ Fink, Sheri (4 February 2015). "Ebola Drug Aids Some in a Study in West Africa". The New York Times.
  15. ↑ Jon Cohen (26 February 2015), "Results from encouraging Ebola trial scrutinized", Science, doi:10.1126/science.aaa7912, retrieved 21 January 2016
  16. ↑ "Favipiravir in Patients with Ebola Virus Disease: Early Results of the JIKI trial in Guinea | CROI Conference". www.croiconference.org. Retrieved 2016-03-17.
  17. ↑ Sissoko, Daouda; Laouenan, Cedric; Folkesson, Elin; M’Lebing, Abdoul-Bing; Beavogui, Abdoul-Habib; Baize, Sylvain; Camara, Alseny-Modet; Maes, Piet; Shepherd, Susan. "Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea". PLOS Medicine 13 (3). doi:10.1371/journal.pmed.1001967. PMC 4773183. PMID 26930627.
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