Study of antiviral agent for RNA virus infection based on favipyravir

• Project/Area Number: 16K09929
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Hokuriku University
• Principal Investigator: DAIKOKU TOHRU 北陸大学, 薬学部, 教授 (80291409)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 抗ウイルス剤 / RNAウイルス / ファビピラビル / 抗ウイルス薬 / ウイルス

Outline of Final Research Achievements

Although favipiravir is approved as an anti-influenza virus drug, it also has antiviral effects of other RNA viruses. The aim of this study is to investigate the most effective compounds for several RNA viruses with favipiravir and its derivatives.
Poliovirus strain Sabin type 1 was used and infected to infection African green monkey kidney cells (Vero cells) in this experiment. The antiviral effect was examined by plaque reduction methods. The drug focused on the 6-position fluorine of favipiravir, and used derivatives substituted with hydrogen, chlorine and bromine.It has been reported that derivatives substituted with hydrogen at position 6 more than favipiravir have higher antiviral effects for influenza viruses, however favipiravir was most effective for poliovirus.

Academic Significance and Societal Importance of the Research Achievements

エボラ出血熱、重症急性呼吸器症候群（SARS）、中東呼吸器症候群（MERS）、黄熱、 デング熱、ジカ熱等はいずれもRNAウイルスによる感染症で、それらのウイルスがいつ日本に持ち込まれてパンデミックを引き起こすかはわからない。ファビピラビルは抗インフルエンザウイルス薬として承認されたが、他のRNAウイルス感染症にも効果が期待されている。RNAウイルスの種類によって、ファビピラビル誘導体の中のどれが一番有効かを調べておく必要がある。今回、種々のファビピラビル誘導体でインフルエンザウイルスとポリオウイルスで比較したが、異なる結果を得た。現在、コロナウイルスやジカウイルスでも同様の検討を行っている。

Research Products

• [Journal Article] The anti-human cytomegalovirus drug tricin inhibits cyclin-dependent kinase 9 (2018)
  • Author(s): Hidetaka Sadanari, Kazuhiro J. Fujimoto, Yuto Sugihara, Tomoki Ishida, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
  • Journal Title: FEBS Open Bio Volume: 8 Issue: 4 Pages: 646-654
  • DOI: 10.1002/2211-5463.12398
  • Peer Reviewed / Open Access
• [Journal Article] Tricin inhibits CCL5 induction required for the efficient growth of human cytomegalovirus (2018)
  • Author(s): Akimasa Itho, Hidetaka Sadanari, Masaya Takemoto, Keiko Matsubara, Tohru Daikoku, Tsugiya Murayama
  • Journal Title: Microbiology and Immunology Volume: 62 Issue: 5 Pages: 341-347
  • DOI: 10.1111/1348-0421.12590
  • NAID: 40021560453
  • Peer Reviewed
• [Journal Article] An in silico-designed flavone derivative, 6-fluoro-4′-hydroxy-3′,5′-dimethoxyflavone, has a greater anti-human cytomegalovirus effect than ganciclovir in infected cells (2018)
  • Author(s): Kazuhiro J. Fujimoto, Daiki Nema, Masayuki Ninomiya, Mamoru Koketsu, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
  • Journal Title: Antivir. Res. Volume: 154 Pages: 10-16
  • DOI: 10.1016/j.antiviral.2018.03.006
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of susceptibility variants of poliovirus grown in the presence of favipiravir (2017)
  • Author(s): Tohru Daikoku, Mineyuki Mizuguchi, Takayuki Obita, Takeshi Yokoyama, Yoshihiro Yoshida, Masaya Takemoto, Kimiyasu Shiraki
  • Journal Title: Journal of Microbiology, Immunology and Infection Volume: 印刷中 Issue: 5 Pages: 30100-7
  • DOI: 10.1016/j.jmii.2017.03.004
  • Peer Reviewed / Open Access
• [Journal Article] T-705 (Favipiravir) suppresses tumor necrosis factor α production in response to influenza virus infection: A beneficial feature of T-705 as an anti-influenza drug (2017)
  • Author(s): T. TANAKA, T. KAMIYAMA, T. DAIKOKU, K. TAKAHASHI, N. NOMURA, M. KUROKAWA, K. SHIRAKI
  • Journal Title: Acta Virologica Volume: 61 Issue: 01 Pages: 48-55
  • DOI: 10.4149/av_2017_01_48
  • Peer Reviewed
• [Journal Article] Subclinical generation of acyclovir-resistant herpes simplex virus with mutation of homopolymeric guanosine strings during acyclovir therapy. (2016)
  • Author(s): Daikoku T, Tannai H, Honda M, Onoe T, Matsuo K, Onoye Y, Nishizawa M, Kawana T, Okuda T, Hasegawa T, Shiraki K.
  • Journal Title: Journal of Dermatological Science Volume: 83 Issue: 3 Pages: 160-165
  • DOI: 10.1016/j.jdermsci.2016.02.006
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ポリオウイルスに対するファビピラビルとその誘導体の効果 (2019)
  • Author(s): 梅田 実希, 藤本 和宏, 亀井 敬, 鎌田 一希, 前崎 将人, 野田 佳加,武本 眞清, 定成 秀貴, 村山 次哉, 大黒 徹
  • Organizer: 日本薬学会