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T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections
A series of pyrazinecarboxamide derivatives T-705 (favipiravir), T-1105 and T-1106 were discovered to be candidate antiviral drugs. These compounds have demonstrated good activity in treating viral infections in laboratory animals caused by various RNA viruses, including influenza virus, arenaviruse...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127082/ https://www.ncbi.nlm.nih.gov/pubmed/19428599 http://dx.doi.org/10.1016/j.antiviral.2009.02.198 |
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author | Furuta, Yousuke Takahashi, Kazumi Shiraki, Kimiyasu Sakamoto, Kenichi Smee, Donald F. Barnard, Dale L. Gowen, Brian B. Julander, Justin G. Morrey, John D. |
author_facet | Furuta, Yousuke Takahashi, Kazumi Shiraki, Kimiyasu Sakamoto, Kenichi Smee, Donald F. Barnard, Dale L. Gowen, Brian B. Julander, Justin G. Morrey, John D. |
author_sort | Furuta, Yousuke |
collection | PubMed |
description | A series of pyrazinecarboxamide derivatives T-705 (favipiravir), T-1105 and T-1106 were discovered to be candidate antiviral drugs. These compounds have demonstrated good activity in treating viral infections in laboratory animals caused by various RNA viruses, including influenza virus, arenaviruses, bunyaviruses, West Nile virus (WNV), yellow fever virus (YFV), and foot-and-mouth disease virus (FMDV). Treatment has in some cases been effective when initiated up to 5–7 days after virus infection, when the animals already showed signs of illness. Studies on the mechanism of action of T-705 have shown that this compound is converted to the ribofuranosyltriphosphate derivative by host enzymes, and this metabolite selectively inhibits the influenza viral RNA-dependent RNA polymerase without cytotoxicity to mammalian cells. Interestingly, these compounds do not inhibit host DNA and RNA synthesis and inosine 5′-monophosphate dehydrogenase (IMPDH) activity. From in vivo studies using several animal models, the pyrazinecarboxamide derivatives were found to be effective in protecting animals from death, reducing viral burden, and limiting disease manifestations, even when treatment was initiated after virus inoculation. Importantly, T-705 imparts its beneficial antiviral effects without significant toxicity to the host. Prompt development of these compounds is expected to provide effective countermeasures against pandemic influenza virus and several bioweapon threats, all of which are of great global public health concern given the current paucity of highly effective broad-spectrum drugs. |
format | Online Article Text |
id | pubmed-7127082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71270822020-04-08 T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections Furuta, Yousuke Takahashi, Kazumi Shiraki, Kimiyasu Sakamoto, Kenichi Smee, Donald F. Barnard, Dale L. Gowen, Brian B. Julander, Justin G. Morrey, John D. Antiviral Res Review A series of pyrazinecarboxamide derivatives T-705 (favipiravir), T-1105 and T-1106 were discovered to be candidate antiviral drugs. These compounds have demonstrated good activity in treating viral infections in laboratory animals caused by various RNA viruses, including influenza virus, arenaviruses, bunyaviruses, West Nile virus (WNV), yellow fever virus (YFV), and foot-and-mouth disease virus (FMDV). Treatment has in some cases been effective when initiated up to 5–7 days after virus infection, when the animals already showed signs of illness. Studies on the mechanism of action of T-705 have shown that this compound is converted to the ribofuranosyltriphosphate derivative by host enzymes, and this metabolite selectively inhibits the influenza viral RNA-dependent RNA polymerase without cytotoxicity to mammalian cells. Interestingly, these compounds do not inhibit host DNA and RNA synthesis and inosine 5′-monophosphate dehydrogenase (IMPDH) activity. From in vivo studies using several animal models, the pyrazinecarboxamide derivatives were found to be effective in protecting animals from death, reducing viral burden, and limiting disease manifestations, even when treatment was initiated after virus inoculation. Importantly, T-705 imparts its beneficial antiviral effects without significant toxicity to the host. Prompt development of these compounds is expected to provide effective countermeasures against pandemic influenza virus and several bioweapon threats, all of which are of great global public health concern given the current paucity of highly effective broad-spectrum drugs. Elsevier B.V. 2009-06 2009-03-06 /pmc/articles/PMC7127082/ /pubmed/19428599 http://dx.doi.org/10.1016/j.antiviral.2009.02.198 Text en Copyright © 2009 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Review Furuta, Yousuke Takahashi, Kazumi Shiraki, Kimiyasu Sakamoto, Kenichi Smee, Donald F. Barnard, Dale L. Gowen, Brian B. Julander, Justin G. Morrey, John D. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections |
title | T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections |
title_full | T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections |
title_fullStr | T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections |
title_full_unstemmed | T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections |
title_short | T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections |
title_sort | t-705 (favipiravir) and related compounds: novel broad-spectrum inhibitors of rna viral infections |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127082/ https://www.ncbi.nlm.nih.gov/pubmed/19428599 http://dx.doi.org/10.1016/j.antiviral.2009.02.198 |
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