Favipiravir

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. Activity against enteroviruses and Rift Valley fever virus has also been demonstrated. Favipiravir showed limited efficacy against Zika virus in animal studies, but was less effective than other antivirals such as MK-608. The agent has also shown some efficacy against rabies, and has been used experimentally in some humans infected with the virus. 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. Activity against enteroviruses and Rift Valley fever virus has also been demonstrated. Favipiravir showed limited efficacy against Zika virus in animal studies, but was less effective than other antivirals such as MK-608. The agent has also shown some efficacy against rabies, and has been used experimentally in some humans infected with the virus. The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase. Other research suggests that favipiravir induces lethal RNA transversion mutations, producing a nonviable viral phenotype. Favipiravir is an orally-administered prodrug and is metabolized to its active form, favipiravir-ribofuranosyl-5'-triphosphate (favipiravir-RTP), following digestion. Human hypoxanthine guanine phosphoribosyltransferase (HGPRT) is believed to play a key role in this activation process. Favipiravir does not inhibit RNA or DNA synthesis in mammalian cells and is not toxic to them. In 2014, favipiravir was approved in Japan for stockpiling against influenza pandemics. However, favipiravir has not been shown to be effective in primary human airway cells, casting doubt on its efficacy in influenza treatment. The drug appears to be effective in a mouse model of Ebola virus disease, but its efficacy against human Ebola infection is unproved. 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. A clinical trial investigating the use of favipiravir against Ebola virus disease was started in Guéckédou, Guinea, during December 2014. 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. The trial design has been criticised by Scott Hammer and others for using only historical controls. 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 and published on March 1, 2016 in PLOS Medicine.