Prof. Dr. Takashi Kuzuhara
Dr. Dai Hatakeyama
Dr. Masaki Shouji
We are studying influenza virus proteins, especially RNA dependent RNA polymerase, NP and NS1. The H1N1 influenza A virus of swine-origin caused pandemics throughout the world in 2009 and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. The threat of influenza thus remains a serious global health issue and novel drugs that target these viruses are highly desirable. Influenza viruses A & B possess RNA dependent RNA polymerase which comprises PA, PB1 and PB2 subunits. We analyze these proteins by biochemistry, molecular biology, protein chemistry, structural biology, molecular interactions, medicinal chemistry, genetics, cellular biology and animal ethology.
1. We revealed the tertiary structure of PB2 pathogenicity-determinant domain.
2. We found the new motif “ϕ structure” in this domain.
3. We found the anti-influenza chemicals: green tea catechins, phenethylphenylphthalimide-analogs, marchantins, C60 fullerene analogs and baluchiol.
We are studying:
1. Chemical modification of influenza virus proteins.
2. Differentiation of iPS cells.
3. Purification and functional analyses of anti-oxidants derived from Awa-ban tea (Tokushima-area-specific fermented tea).
- Shoji M, Nishioka M, Minato H, Harada K, Kubo M, Fukuyama Y, Kuzuhara T. Neurotrophic activity of jiadifenolide on neuronal precursor cells derived from human induced pluripotent stem cells. Biochemical and Biophysical Research Communications, 470 (4), 2016, 798–803.
- Shoji M, Arakaki Y, Esumi T, Kohnomi S, Yamamoto C, Suzuki Y, Takahashi E, Konishi S, Kido H, Kuzuhara T. Bakuchiol is a Phenolic Isoprenoid with Novel Enantiomer-Selective Anti-Influenza A Virus Activity Involving Nrf2 Activation. J. Biol. Chem., 290(46), 28001-28017, 2015.
- Hatakeyama D, Shoji M, Yamayoshi S, Hirota T, Nagae M, Yanagisawa S, Nakano M, Ohmi N, Noda T, Kawaoka Y, Kuzuhara T. A novel functional site in the PB2 subunit of influenza A virus essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication. J. Biol. Chem. 2014 Sep 5; 289 (36): 24980-24994.
- Miki Hiasa, Megumi Kurokawa, Hiroshi Akita, Masatomo Harada, Kengo Niki, Kana Ohta, Masaki Shoji, Noriko Echigo, Takashi Kuzuhara, Suppression of increased blood glucose levels in mice by Awa-ban tea following oral administration of mono- and disaccharides, Journal of Functional Foods, 8, 188–192 (2014).
- Hiasa M, Isoda Y, Kishimoto Y, Saitoh K, Kimura Y, Kanai M, Shibasaki M, Hatakeyama D, Kirino Y, Kuzuhara T.Inhibition of monoamine oxidase A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir. British Journal of Pharmacology, 169, 115–129, (2013).
- Hiasa M, Kurokawa M, Ohta K, Esumi T, Akita H, Niki K, Yagi Y, Echigo N, Hatakeyama D, Kuzuhara T. Identification and purification of resorcinol, an antioxidant specific to Awa-ban (pickled and anaerobically fermented) tea. Food Research International, 54, 72-80 (2013).
- Tsurumura T, Qiu H, Yoshida T, Tsumori Y, Hatakeyama D, Kuzuhara T, Tsuge H., Conformational Polymorphism of m(7)GTP in Crystal Structure of the PB2 Middle Domain from Human Influenza A Virus. PLoS One. 8(11): e82020, (2013).
- Iwai Y, Murakami K, Gomi Y, Hashimoto T, Asakawa Y, Okuno Y, Ishikawa T, Hatakeyama D, Echigo N, Kuzuhara T.; Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts., PLoS One, 6(5), e19825 (2011).
- Ludwiczuk A, Saha A, Kuzuhara T, Asakawa Y.; Bioactivity guided isolation of anticancer constituents from leaves of Alnus sieboldiana (Betulaceae). Phytomedicine, 18(6): 491-498 (2011).
- Saha A., Kuzuhara T., Echigo N., Fujii A., Suganuma M., Fujiki H.; Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of growth arrest and DNA damage inducible genes 45 and 153. Biol. Pharm. Bull., 33(8):1291-1299 (2010).
- Saha A., Kuzuhara T. Echigo N., Suganuma M., Fujiki H.; New Role of (-)-Epicatechin in Enhancing the Induction of Growth Inhibition and Apoptosis in Human Lung Cancer Cells by Curcumin. Cancer Prev. Res., 3(8):953-962 (2010).
- Iwai Y, Takahashi H, Hatakeyama D, Motoshima K, Ishikawa M, Sugita K, Hashimoto Y, Harada Y, Itamura S, Odagiri T, Tashiro M, Sei Y, Yamaguchi K, Kuzuhara T.; Anti-influenza Activity of Phenethylphenylphthalimide Analogs Derived from Thalidomide. Bioorg. Med. Chem., 18, 5379-5390 (2010).