Effect of a novel resistance associated mutation, N348I, which has been identified in Japanese HIV-1 infected patients, on the reverse transcriptase activity.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Tohoku University
• Principal Investigator: KODAMA Eiichi 東北大学, 病院, 助教 (50271151)
• Project Period (FY): 2009 – 2011
• Keywords: ウイルス / HIV / 薬剤耐性 / 逆転写酵素 / 多剤耐性

Research Abstract

Effect of a novel resistance associated mutation, N348I, which has been identified in Japanese HIV-1 infected patients, on the reverse transcriptase activity.

Research Products

• [Journal Article] Biochemical, inhibition, and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase (2012)
  • Author(s): Tanyaradzwa P. Ndongwe, Adeyemi O. Adedeji, Eleftherios Michailidis, Yee Tsuey Ong, Atsuko Hachiya, Bruno Marchand, Emily M. Ryan, Devendra K. Rai, Karen A. Kirby, Angela S. Whatley, Donald H. Burke, Marc Johnson, Shilei Ding, Yi-Min Zheng, Shan-Lu Liu, E
  • Journal Title: Nucleic Acids Research Volume: 40 Pages: 345-359
  • Peer Reviewed
• [Journal Article] Potent anti-HIV-1 activity of N-HR-derived peptides including a deep pocket-forming region without antagonistic effect on T-20 (2011)
  • Author(s): Kazuki Izumi, Kentaro Watanabe, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka, Stefan G. Sarafianos and Eiichi N. Kodama
  • Journal Title: Antiviral Chemistry and Chemotherapy Volume: 22 Pages: 51-55
  • Peer Reviewed
• [Journal Article] Epigallocatechin gallate inhibits HIV reverse transcription step (2011)
  • Author(s): Shenwei Li, Toshio Hattori, Eiichi N Kodama
  • Journal Title: Antiviral Chemistry and Chemotherapy Volume: 21 Pages: 239-243
  • Peer Reviewed
• [Journal Article] The sugar ring conformation of 4'-ethynyl-2-fluoro-2'-deoxyadenosine and its recognition by the polymerase active site of HIV reverse transcriptase (2011)
  • Author(s): Karen A. Kirby, Kamalendra Singh, Eleftherios Michailidis, Bruno Marchand, Eiichi N. Kodama, Noriyuki Ashida, Hiroaki Mitsuya, Michael A. Parniak, Stefan G. Sarafianos
  • Journal Title: Cellular and Molecular Biology Volume: 57 Pages: 39-44
  • Peer Reviewed
• [Journal Article] K70Q adds high-level tenofovir resistance to"Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism (2011)
  • Author(s): Atsuko Hachiya, Eiichi N. Kodama, Matthew M. Schuckmann, Karen A. Kirby, Eleftherios Michailidis, Yasuko Sakagami, Shinichi Oka, Kamalendra Singh, Stefan G. Sarafianos
  • Journal Title: PLoS One Volume: 6 Pages: 16242
  • Peer Reviewed
• [Journal Article] Resistance profiles of novel electrostatically constrained HIV-1 fusion inhibitors (2010)
  • Author(s): Kazuya Shimura, Daisuke Nameki, Keiko Kajiwara, Kentaro Watanabe, Yasuko Sakagami, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka, Stefan G. Sarafianos, Eiichi N. Kodama
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 39471-39480
  • Peer Reviewed
• [Journal Article] The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine (2010)
  • Author(s): Matthew Michael Schuckmann, Bruno Marchand, Atsuko Hachiya, Eiichi N. Kodama, Karen A. Kirby, Kamalendra Singh, Stefan G. Sarafianos
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 38700-38709
  • Peer Reviewed
• [Journal Article] Affinity selection and sequence-activity relationships of HIV-1 membrane fusion inhibitors directed at the drug-resistant variants (2010)
  • Author(s): Shinya Oishi, Kentaro Watanabe, Saori Ito, Michinori Tanaka, Hiroki Nishikawa, Hiroaki Ohno, Kazuki Shimane, Kazuki Izumi, Yasuko Sakagami, Eiichi N. Kodama, Masao Matsuoka, Akira Asai and Nobutaka Fujii
  • Journal Title: Medicinal Chemistry Communications Volume: 1 Pages: 276-281
  • Peer Reviewed
• [Journal Article] Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor, CXCR4 (2010)
  • Author(s): Kazuki Shimane, Eiichi N. Kodama, Ikuhiko Nakase, Shiroh Futaki, Yasuteru Sakurai, Yasuko Sakagami, Xiaoguang Li, Toshio Hattori, Stefan G. Sarafianos, Masao Matsuoka
  • Journal Title: International Journal of Biochemistry and Cell Biology Volume: 42 Pages: 1482-1488
  • Peer Reviewed
• [Journal Article] Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino terminal heptad repeat (2010)
  • Author(s): Kazuki Izumi, Shota Nakamura, Hiroaki Nakano, Kazuya Shimura, Yasuko Sakagami, Shinya Oishi, Susumu Uchiyama, Tadayasu Ohkubo, Yuji Kobayashi, Nobutaka Fujii, Masao Matsuoka, Eiichi N. Kodama
  • Journal Title: Antiviral Research Volume: 87 Pages: 179-186
  • Peer Reviewed
• [Journal Article] Procyanidin B-1 purified from Cinnamomi Cortex suppresses HCV replication (2010)
  • Author(s): Shenwei Li, Eiichi N Kodama, Yuuki Inoue, Hideki Tani, Yoshiharu Matsuura, Jing Zhang, Takashi Tanaka, Toshio Hattori
  • Journal Title: Antiviral Chemistry and Chemotherapy Volume: 20 Pages: 239-248
  • Peer Reviewed
• [Journal Article] Binding of Multivalent Anionic Porphyrins to V3 Loop Fragments of HIV-1 gp120 and Their Antiviral Activity (2010)
  • Author(s): Kenji Watanabe, Shigeru Negi, Yukio Sugiura, Akiko Kiriyama, Akino Honbo, Katsumi Iga, Eiichi N. Kodama, Takeshi Naitoh, Masao Matsuoka, and Koji Kano
  • Journal Title: Chemistry-An Asian Journal Volume: 5 Pages: 825-834
  • Peer Reviewed
• [Journal Article] Synthesis and Biological Evaluation of Selective CXCR4 Antagonists Containing Alkene Dipeptide Isosteres (2010)
  • Author(s): Tetsuo Narumi, Ryoko Hayashi, Kenji Tomita, Kazuya Kobayashi, Noriko Tanahara, Hiroaki Ohno, Takeshi Naito, Eiichi Kodama, Masao Matsuoka, Shinya Oishi, and Nobutaka Fujii
  • Journal Title: Organic & Biomolecular Chemistry Volume: 8 Pages: 616-621
  • Peer Reviewed
• [Journal Article] Mechanism of inhibition of HIV-1 reverse transcriptase by 4'-ethynyl-2-fluoro-2'-doxyadenosine triphosphate, a translocation defective reverse transcriptase inhibitor (2009)
  • Author(s): Eleftherios Michailidis, Bruno Marchand, Eiichi N. Kodama, Kamlendra Singh, Masao Matsuoka, Karen A. Kirby, Emily M. Ryan, Ali M. Sawani, Eva Nagy, Noriyuki Ashida, Hiroaki Mitsuya, Michael A. Parniak, and Stefan G. Sarafianos
  • Journal Title: Journal of Biological Chemistry Volume: 284 Pages: 35681-35691
  • Peer Reviewed
• [Journal Article] Bioorganic Synthesis of a Recombinant HIV-1 Fusion Inhibitor, SC35EK, with an N-Terminal Pyroglutamate Capping Group (2009)
  • Author(s): Kazumi Kajiwara, Kentaro Watanabe, Rei Tokiwa, Tomoko Kurose, Hiroaki Ohno, Hiroko Tsutsumi, Yoji Hata, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Shinya Oishi, and Nobutaka Fujii
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 17 Pages: 7964. 7970
  • Peer Reviewed
• [Journal Article] Bioorganic Synthesis of End-capped Anti-HIV Peptides by Simultaneous Cyanocysteine-mediated Cleavages of Recombinant Proteins (2009)
  • Author(s): Michinori Tanaka, Kazumi Kajiwara, Rei Tokiwa, Kentaro Watanabe, Hiroaki Ohno, Hiroko Tsutsumi, Yoji Hata, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Shinya Oishi, Nobutaka Fujii
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 17 Pages: 7487-7492
  • Peer Reviewed
• [Journal Article] X-ray Crystallographic Study of an HIV-1 Fusion Inhibitor with the gp41 S138A Substitution (2009)
  • Author(s): Tsuyoshi Watabe, Yukihiro Terakawa, Kentaro Watanabe, Hiroaki Ohno, Hiroaki Nakano, Toru Nakatsu, Hiroaki Kato, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Kazuo Kitaura, Shinya Oishi, Nobutaka Fujii
  • Journal Title: Journal of Molecular Biology Volume: 392 Pages: 657-665
  • Peer Reviewed
• [Journal Article] Design and synthesis of membrane fusion inhibitors against the feline immunodeficiency virus (2009)
  • Author(s): Shinya Oishi, Yasuyo Kodera, Hiroki Nishikawa, Kamitani H, Tsuyoshi Watabe, Hiroaki Ohno, Tadafumi Tochikura, Kazuki Shimane, Eiichi Kodama, Masao Matsuoka, Fuminori Mizukoshi, Hajime Tsujimoto H, Nobutaka Fujii
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 17 Pages: 4916-4920
  • Peer Reviewed
• [Journal Article] Peptide bond mimicry by(E)-alkene and(Z)-fluoroalkene peptide isosteres : synthesis and bioevaluation of alpha-helical anti-HIV peptide analogues (2009)
  • Author(s): Shinya Oishi, Hirotaka Kamitani, Yasuyo Kodera, KentaroWatanabe, Kazuya Kobayashi, Tetsuo Narumi, Kenji Tomita, Hiroaki Ohno, Takeshi Naito, Eiichi Kodama, Masao Matsuoka and Nobutaka Fujii
  • Journal Title: Organic & Biomolecular Chemistry Volume: 7 Pages: 2872-2877
  • Peer Reviewed
• [Journal Article] Clinical relevance of substitutions in the connection subdomain and RNase H domains of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients (2009)
  • Author(s): Atsuko Hachiya, Kazuki Shimane, Stefan G. Sarafianos, Eiichi N. Kodama, Yasuko Sakagami, Fujie Negishi, Hirokazu Koizumi, Hiroyuki Gatanaga, Masao Matsuoka, Masafumi Takiguchi, Shinichi Oka
  • Journal Title: Antiviral Research Volume: 82 Pages: 115-121
  • Peer Reviewed
• [Presentation] Development of HIV-1 fusion inhibitors active to enfuvirtide resistant variants (2011)
  • Author(s): Eiichi N. Kodama
  • Organizer: US-Japan Joint AIDS Panel : Resistance Meeting, Singapore
  • Place of Presentation: Invited
  • Year and Date: 20111208-10
• [Presentation] Effect of 4'-and2-NRTI Substitutions on the Inhibition Mechanism of HIV Reverse Transcriptase (2011)
  • Author(s): Eleftherios Michailidis, Stephen H. Hughes, Emily M. Ryan, Atsuko Hachiya, Devendra Rai, Jordan Wilkins, Kamlendra Singh, Bruno Marchand, Mark Hannink, B. Christie Vu, Victor Marquez, Ei-Ichi Kodama, Hiroaki Mitsuya, Michael A. Parniak, and Stefan G. Sara
  • Organizer: 12th Annual Symposium on Antiviral Drug Resistance, Hershey, Pennsylvania
  • Place of Presentation: USA
  • Year and Date: 20111106-09
• [Presentation] HIV-1 Reverse Transcriptase(RT)Polymorphism 172K Suppresses the Effect of Clinically Relevant Drug Resistance Mutations to Both Nucleoside and Nonnucleoside RT Inhibitors (2011)
  • Author(s): Atsuko Hachiya, Bruno Marchand, Karen A. Kirby, Eleftherios Michailidis, Xiongying Tu, Yee Tsuey Ong, Daniel T. Griffin, Matthew M. Schuckmann, Junko Tanuma, Shinichi Oka, Kamalendra Singh, Eiichi N. Kodama and Stefan G. Sarafianos
  • Organizer: 12th Annual Symposium on Antiviral Drug Resistance, Hershey, Pennsylvania
  • Place of Presentation: USA
  • Year and Date: 20111106-09
• [Presentation] HIV-1 Reverse Transcriptase Polymorphism 172K Suppresses the Effect of Clinical Resistance Mutations to both NRTI and NNRTI (2011)
  • Author(s): Atsuko Hachiya, Matthew M. Schuckmann, D Griffin, Karen A. Kirby, YT Ong Junko Tanuma, Shinichi Oka, Kamlendra Singh, Eiichi N. Kodama, Stefan G. Sarafianos
  • Organizer: 8th conference on retroviruses and opportunistic infections Boston, MA
  • Place of Presentation: USA
  • Year and Date: 20110227-0502
• [Presentation] K70Q expands multi-drug resistance(MDR)of HIV-1 containing"Q151M complex" reverse transcriptase mutations (2009)
  • Author(s): Atsuko Hachiya, Eiichi N. Kodama, Matthew M. Schuckmann, Karen A. Kirby, Eleftherios Michailidis, Yasuko Sakagami, Kamlendra Singh, Shinichi Oka, and Stefan G. Sarafianos
  • Organizer: 10th Annual Symposium on Antiviral Drug Resistance, Richmond, VA
  • Place of Presentation: USA
  • Year and Date: 20091115-18
• [Presentation] The NNRTI-resistant Y181C HIV-1 reverse transcriptase is hyper-susceptible to 4'-ethynyl-2-fluoro deoxyadenosine(EFDA) (2009)
  • Author(s): Yee Tsuey Ong, Eleftherios Michailidis, Bruno Marchand, Matthew S. Schuckmann, Kamlendra Singh, Ei-Ichi Kodama, Masao Matsuoka, Hiroaki Mitsuya, Eva Nagy, Michael A. Parniak, and Stefan G. Sarafianos
  • Organizer: 10th Annual Symposium on Antiviral Drug Resistance, Richmond, VA
  • Place of Presentation: USA
  • Year and Date: 20091115-18
• [Presentation] Biochemical characterization of the HIV reverse transcriptase connection domain multi-class drug resistance mutation N348I (2009)
  • Author(s): Matthew Schuckmann, Atsuko Hachiya, Ei-ichi N. Kodama, Bruno Marchand, Eleftherios Michailidis, Kamlendra Singh, Yasuko Sakagami, Shinichi Oka, and Stefan G. Sarafianos
  • Organizer: 10th Annual Symposium on Antiviral Drug Resistance, Richmond, VA
  • Place of Presentation: USA
  • Year and Date: 20091115-18
• [Presentation] Parniak 4'-Ethynyl-2-fluoro-2'-deoxyadenosine(EFDA), a translocation defective reverse transcriptase inhibitor with highly potent activity against diverse multi-drug-resistant HIV-1 variants (2009)
  • Author(s): Hiroaki Mitsuya, Stefan G. Sarafianos, Eiichi Kodama, Hirotomo Nakata, Seiji Okada, and Michael A
  • Organizer: 10th Annual Symposium on Antiviral Drug Resistance, Richmond, VA
  • Place of Presentation: USA
  • Year and Date: 20091115-18
• [Presentation] Drug design for resistant HIV (2009)
  • Author(s): Kodama E
  • Organizer: 10th Kumamoto AIDS seminar/AIDS GCOE International Symposium Satellite symposium, Kumamoto, Japan
  • Place of Presentation: Invited
  • Year and Date: 2009-09-30
• [Remarks]
  • URL: http://www.rid.med.tohoku.ac.jp/index.html