Study of generation and dynamics of HIV enzymes essential for replication and structural design of their inhibitors

• Project/Area Number: 20390288
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Kumamoto University
• Principal Investigator: MITSUYA Hiroaki Kumamoto University, 大学院・生命科学研究部, 教授 (20136724)
• Research Collaborator: GHOSH Arun K. 米国Purdue大学, 教授 ; ARNOLD Eddy 米国Rutgers大学, 教授 ; KOVARI Ladislau 米国Wayne州立大学, 教授
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 感染症 / HIV / エイズ / HIV酵素二量体化阻害剤 / 創薬 / 薬剤耐性 / 新規抗HIV化合物 / HIV蛋白の自壊

Research Abstract

We reported in this study period that, through superinfection of cells with multiple HIV-1 strains and homologous recombination, HIV-1 can acquire high-level resistance against darunavir (DRV), to which HIV-1 hardly acquires resistance. We also identified cyclopentanyl-tetrahydrofuran-containing GRL-02031, which binds to HIV-1 protease in a bimodal way and exerts potent antiviral activity. Furthermore, we obtained GRL-0216A and -0286A with a macrocyclic ligand plus GRL-1388A and -1398A which contain a tetrahydropyrano-tetrahydrofuran moiety and exert potenta activity agaisnt multi-drug resistant varinats including DRV-resistant HIV-1 strains. We also ideintified GRL-0519A, which contains an oxatricyclic-tetrahydrofuran with potent anti-HIV activtiy agaisnt a wide spectrum of drug-resistant HIV-1s and potent activity to block the dimerization of HIV-1 portease monomers.

Research Products

• [Journal Article] Design, Synthesis, and X-ray Structure of Substituted bis-tetrahydrofuran (bis-THF)- Derived Potent HIV-1 Protease Inhibitors. (2011)
  • Author(s): Ghosh AK, Martyr CD, Steffey M, Wang YF, Agniswamy J, Amano M, Weber IT, Mitsuya H
  • Journal Title: ACS Med.Chem.Lett 2 Pages: 298-302
  • Peer Reviewed
• [Journal Article] Novel HIV-1 Protease Inhibitors (PIs) Containing a Bicyclic P2 Functional Moiety, Tetrahydropyrano-Tetrahydrofuran, That Are Potent against Multi-PI-Resistant HIV-1 Variants. (2011)
  • Author(s): Ide K, Aoki M, Amano M, Koh Y, Yedidi RS, Das D, Leschenko S, Chapsal B, Ghosh AK, Mitsuya H
  • Journal Title: Antimicrob Agents Chemother. 55 Pages: 1717-1787
  • Peer Reviewed
• [Journal Article] Design and synthesis of potent HIV-1 protease inhibitors incorporating Hexahydrofuropyranolderived high affinity P(2) ligands : structure-activity studies and biological evaluation. (2011)
  • Author(s): Ghosh AK, Chapsal BD, Baldridge A, Steffey MP, Walters DE, Koh Y, Amano M, Mitsuya H.
  • Journal Title: J Med Chem. 27;54(2) Pages: 622-634
  • Peer Reviewed
• [Journal Article] Design, Synthesis, and X-ray Structure of Substituted bis-tetrahydrofuran (bis-THF)-Derived Potent HIV-1 Protease Inhibitors. (2011)
  • Author(s): Ghosh AK, Martyr CD, Steffey M, Wang YF, Agniswamy J, Amano M, Weber IT, Mitsuya H
  • Journal Title: ACS Med.Chem.Lett. Volume: 2 Pages: 298-302
  • Peer Reviewed
• [Journal Article] Novel HIV-1 Protease Inhibitors (PIs) Containing a Bicyclic P2 Functional Moiety, Tetrahydropyrano- Tetrahydrofuran, That Are Potent against Multi-PI -Resistant HIV-1 Variants. (2011)
  • Author(s): Ide K, Aoki M, Amano M, Koh Y, Yedidi RS, Das D, Leschenko S, Chapsal B, Ghosh AK, Mitsuya H
  • Journal Title: Antimicrob Agents Chemother. Volume: 55 Pages: 1717-1787
  • Peer Reviewed
• [Journal Article] Design and synthesis of potent HIV-1 protease inhibitors incorporating Hexahydrofuropyranol-derived high affinity P(2)ligands : structure-activity studies and biological evaluation. (2011)
  • Author(s): Ghosh AK, Chapsal BD, Baldridge A, Steffey MP, Walters DE, Koh Y, Amano M, Mitsuya H
  • Journal Title: J Med Chem. Volume: 27;54(2) Pages: 622-634
  • Peer Reviewed
• [Journal Article] Probing multidrug-resistance and protein-ligand interactions with oxatricyclic designed ligands in HIV-1 protease inhibitors. (2010)
  • Author(s): Ghosh AK, Xu CX, Rao KV, Baldridge A, Agniswamy J, Wang YF, Weber IT, Aoki M, Miguel SG, Amano M, Mitsuya H.
  • Journal Title: ChemMedChem. 5 Pages: 1850-1854
  • Peer Reviewed
• [Journal Article] In vitro selection of highly darunavir-resistant and replicationcompetent HIV-1 variants using a mixture of clinical HIV-1 isolates resistant to multiple conventional protease inhibitors. (2010)
  • Author(s): Koh Y, Amano M, Towata T, Danish M, Leshchenko-Yashchuk S, Das D, Nakayama M, Tojo Y, Ghosh AK, Mitsuya H.
  • Journal Title: J Virol. 84 Pages: 11961-11969
  • Peer Reviewed
• [Journal Article] Novel protease inhibitors (PIs) containing macrocyclic components and 3(R),3a(S),6a(R)-bis tetrahydrofuranylurethane that are potent against multi-PI-resistant HIV-1 variants in vitro. (2010)
  • Author(s): Tojo Y, Koh Y, Amano M, Aoki M, Das D, Kulkarni S, Anderson DD, Ghosh AK, Mitsuya H.
  • Journal Title: Antimicrob Agents Chemother. 54 Pages: 3460-3470
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands. (2010)
  • Author(s): Ghosh AK, Gemma S, Simoni E, Baldridge A, Walters DE, Ide K, Tojo Y, Koh Y, Amano M, Mitsuya H.
  • Journal Title: Bioorg Med Chem Lett. 20 Pages: 1241-1246
  • Peer Reviewed
• [Journal Article] Probing multidrug-resistance and protein-ligand interactions with oxatricyclic designed ligands in HIV-1 protease inhibitors. (2010)
  • Author(s): Ghosh AK, Xu CX, Rao KV, Baldridge A, Agniswamy J, Wang YF, Weber IT, Aoki M, Miguel SG, Amano M, Mitsuya H
  • Journal Title: ChemMedChem. Volume: 5 Pages: 1850-1854
  • Peer Reviewed
• [Journal Article] In vitro selection of highly darunavir-resistant and replication-competent HIV-1 variants using a mixture of clinical HIV-1 isolates resistant to multiple conventional protease inhibitors. (2010)
  • Author(s): Koh Y, Amano M, Towata T, Danish M, Leshchenko-Yashchuk S, Das D, Nakayama M, Tojo Y, Ghosh AK, Mitsuya H
  • Journal Title: J Virol. Volume: 84 Pages: 11961-969
  • Peer Reviewed
• [Journal Article] Novel protease inhibitors (PIs) containing macrocyclic components and 3(R), 3a(S), 6a(R)-bis- tetrahydrofuranylurethane that are potent against multi-PI-resistant HIV-1 variants in vitro. (2010)
  • Author(s): Tojo Y, Koh Y, Amano M, Aoki M, Das D, Kulkarni S, Anderson DD, Ghosh AK, Mitsuya H
  • Journal Title: Antimicrob Agents Chemother. Volume: 54 Pages: 3460-3470
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands. (2010)
  • Author(s): Ghosh AK, Gemma S, Simoni E, Baldridge A, Walters DE, Ide K, Tojo Y, Koh Y, Amano M, Mitsuya H
  • Journal Title: Bioorg Med Chem Lett. Volume: 20 Pages: 1241-1246
  • Peer Reviewed
• [Journal Article] Effects of CCR5 Inhibitors on the Dynamics of CCR5 and CC-chemo kine-CCR5 interactions (2010)
  • Author(s): Nakata, H., Mitsuya, H., et al.
  • Journal Title: Antiviral Therapy (in press)
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of novel allophenyl-norsta tine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands (2010)
  • Author(s): Ghosh, AK, Mitsuya, H., et al.
  • Journal Title: Bioorg.Med.Chem.Lett 20 Pages: 1241-1246
  • Peer Reviewed
• [Journal Article] Effects of CCR5 Inhibitors on the Dynamics of CCR5 and CC-chemokine-CCR5 interactions. (2009)
  • Author(s): Nakata H, Kruhlak M, Kamata W, Ogata-Aoki H, Li J, Maeda K, Ghosh AK, Mitsuya H.
  • Journal Title: Antivir Ther. 15 Pages: 321-331
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands. (2009)
  • Author(s): Ghosh AK, Gemma S, Simoni E, Baldridge A, Walters DE, Ide K, Tojo Y, Koh Y, Amano M, Mitsuya H.
  • Journal Title: J.Med.Chem. 20 Pages: 1241-1246
  • Peer Reviewed
• [Journal Article] Prediction of Potency of Protease Inhibitors Using Free Energy Simulations with Polarizable Quantum Mechanics-Based Ligand Charges and a Hybrid Water Model. (2009)
  • Author(s): Das D, Koh Y, Tojo Y, Ghosh AK, Mitsuya H.
  • Journal Title: J.Chem.Inf.Model. 49 Pages: 2851-2862
  • Peer Reviewed
• [Journal Article] Design, Synthesis, Protein-Ligand X-ray Structure, and Biological Evaluation of a Series of Novel Macrocyclic Human Immunodeficiency Virus-1 Protease Inhibitors to Combat Drug Resistance. (2009)
  • Author(s): Ghosh AK, Kulkarni S, Anderson DD, Hong L, Baldridge A, Wang YFChumanevich AA, Kovalevsky AY, Tojo Y, Amano M, Koh Y, Tang J, Weber IT, Mitsuya H.
  • Journal Title: J.Med.Chem. 52 Pages: 7689-7705
  • Peer Reviewed
• [Journal Article] Non-cleavage Site Gag Mutations in Amprenavir-resistant HIV-1 Predispose HIV-1 to Rapid Acquisition of Amprenavir Resistance But Delays Development of Resistance to Other Protease Inhibitors. (2009)
  • Author(s): Aoki M, David JV, Koh Y, Aoki-Ogata H, Miyakawa T, Yoshimura K, Maeda K, Mitsuya H.
  • Journal Title: J Virol. 83 Pages: 3059-3068
  • Peer Reviewed
• [Journal Article] GRL-02031 : A Novel Nonpeptidic Protease Inhibitor (PI) Containing A Stereochemically Defined Fused Cyclopentanyltetrahydrofuran (Cp-THF) Potent Against Multi-PI-Resistant HIV-1 In Vitro. (2009)
  • Author(s): Koh Y, Das D, Leschenko S, Nakata H, Ogata-Aoki H, Amano M, Nakayama M, Ghosh AK, Mitsuya H.
  • Journal Title: Antimicrob Agents Chemother. 53 Pages: 997-1006
  • Peer Reviewed
• [Journal Article] Design of HIV-1 protease inhibitors with pyrrolidinones and oxazolidinones as novel Pl'-ligands to enhance backbone-binding interactions with protease : synthesis, biological evaluation, and protein-ligand X-ray studies (2009)
  • Author(s): Ghosh, AK, Mitsuya, H., et al.
  • Journal Title: J.Med.Chem 52 Pages: 3902-3914
  • Peer Reviewed
• [Journal Article] P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines (2009)
  • Author(s): Fujimoto H, Mitsuya, H., et al.
  • Journal Title: Biol.Pharm.Bull. 32 Pages: 1588-1593
  • NAID: 130000117288
  • Peer Reviewed
• [Journal Article] Design, synthesis, protein-ligand X-ray structures and biological evaluation of a series of novel macrocyclic HIV-1 protease inhibitors to combat drug-resistance (2009)
  • Author(s): Ghosh, AK, Mitsuya, H., et al.
  • Journal Title: J.Med.Chem 52 Pages: 7689-7705
  • Peer Reviewed
• [Journal Article] Potent activity of a nucleoside reverse transcriptase inhibitor, 4'-ethynyl-2-fluoro-2'-deoxyadenosine, against HIV-1 infection in Hu-PBMC-NOD/ SCID/JAK3null(NOJ)mouse model (2009)
  • Author(s): Hattori S, Mitsuye, H., et al.
  • Journal Title: Antimicrob.Agents Chemother 53 Pages: 3887-3893
  • Peer Reviewed
• [Journal Article] Prediction of Potency of Protease Inhibitors Using Free Energy Simulations with Polarizable Quantum Mechanics-Based Ligand Charges and a Hybrid Water Model (2009)
  • Author(s): Das D, Mitsuya, H., et al.
  • Journal Title: J.Chem.Inf.Model 49 Pages: 2851-2862
  • Peer Reviewed
• [Journal Article] Mechanism of inhibition of HIV-1 reverse transcriptase by 4'-ethynyl-2-fluoro-deoxyadenosine triphosphate, a translocation defective reverse transcriptase inhibitor (2009)
  • Author(s): Michailidis E, Mitsuya, H., et al.
  • Journal Title: J.Biol.Chem. 284 Pages: 35681-35691
  • Peer Reviewed
• [Journal Article] GRL-02031, a novel nonpeptidic protease inhibitor (PI)containing a stereochemically defined fused cyclopentanyltetrahydrofuran potent against multi-PI-resistant human immunodeficiency virus type 1 in vitro. (2009)
  • Author(s): Koh Y
  • Journal Title: Antimicrob Agents Chemother. 53 Pages: 997-1006
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Stereochemically Defined Novel Spirocyclic P2-Ligands for HIV-1 Protease Inhibitors. (2008)
  • Author(s): Ghosh AK, Chapsal BD, Baldridge A, Ide K, Koh Y, Mitsuya H.
  • Journal Title: Org Lett. 10 Pages: 5135-5138
  • Peer Reviewed
• [Journal Article] Potent HIV-1 protease inhibitors incorporating meso-bicyclic urethanes as P2-ligands : structure-based design, synthesis, biological evaluation and protein-ligand X-ray studies. (2008)
  • Author(s): Ghosh AK, Gemma S, Takayama J, Baldridge A, Leshchenko-Yashchuk S, Miller HB, Wang YF, Kovalevsky AY, Koh Y, Weber IT, Mitsuya H.
  • Journal Title: Org Biomol Chem. 6 Pages: 3703-3713
• [Journal Article] Flexible cyclic ethers/ polyethers as novel P2-ligands for HIV-1 protease inhibitors : design, synthesis, biological evaluation, and protein-ligand X-ray studies. (2008)
  • Author(s): Ghosh AK, Gemma S, Baldridge A, Wang YF, 5 Kovalevsky AY, Koh Y, Weber IT, Mitsuya H.
  • Journal Title: J Med Chem. 51 Pages: 6021-6033
  • Peer Reviewed
• [Journal Article] Involvement of the second extracellular loop and transmembrane residues of CCR5 in inhibitor binding and HIV-1 fusion : insights into the mechanism of allosteric inhibition. (2008)
  • Author(s): Maeda K, Das D, Yin PD, Tsuchiya K, Ogata-Aoki H, Nakata H, Norman RB, Hackney LA, Takaoka Y, Mitsuya H.
  • Journal Title: J Mol Biol. 381 Pages: 956-974
  • Peer Reviewed
• [Journal Article] Potent synergistic anti-human immunodeficiency virus (HIV) effects using combinations of the CCR5 inhibitor aplaviroc with other anti-HIV drugs. (2008)
  • Author(s): Nakata H, Steinberg SM, Koh Y, Maeda K, Takaoka Y, Tamamura H, Fujii N, Mitsuya H.
  • Journal Title: Antimicrob Agents Chemother. 52 Pages: 2111-2119
  • Peer Reviewed
• [Journal Article] Development of protease inhibitors and the fight with drug-resistant HIV-1 variants. (2008)
  • Author(s): Mitsuya H, Maeda K, Das D, Ghosh AK.
  • Journal Title: Adv Pharmacol. 56 Pages: 169-197
  • Peer Reviewed
• [Journal Article] Design of HIV protease inhibitors targeting protein backbone : an effective strategy for combating drug resistance. (2008)
  • Author(s): Ghosh AK, Chapsal BD, Weber IT, Mitsuya H.
  • Journal Title: Acc Chem Res. 41 Pages: 78-86
  • Peer Reviewed
• [Journal Article] Development of protease inhibitors and the fight with drug-resistant HIV-1 variants. (2008)
  • Author(s): Mitsuya H
  • Journal Title: Adv Pharmacol. 56 Pages: 169-197
• [Journal Article] Design of HIV protease inhibitors targeting protein backbone : an effective strategy for combating drug resistance. (2008)
  • Author(s): Ghosh AK
  • Journal Title: Ace Chem Res. 41 Pages: 78-86
  • Peer Reviewed
• [Journal Article] Flexible cyclic ethers/polyethers as novel P2-ligands for HIV-1 protease inhibitors : design, synthesis, biological evaluation, and protein-ligand X-ray studies. (2008)
  • Author(s): Ghosh AK
  • Journal Title: J Med Chem. 51 Pages: 6021-6033
  • Peer Reviewed
• [Journal Article] Potent HIV-1 protease inhibitors incorporating meso-bicyclic urethanes as P2-ligands : structure-based design, synthesis, biological evaluation and protein-ligand X-ray studies. (2008)
  • Author(s): Ghosh AK
  • Journal Title: Org Biomol Chem. 6 Pages: 3703-3713
  • Peer Reviewed
• [Journal Article] Design and synthesis of stereochemically defined novel spirocyclic P2-ligands for HIV-1 protease inhibitors. (2008)
  • Author(s): Ghosh AK
  • Journal Title: Org Lett. 10 Pages: 5135-5138
  • Peer Reviewed
• [Presentation] Mechanism of the Emergence of HIV-1 Variants Highly Resistant to Darunavir. (2010)
  • Author(s): Matthew L.Danish, Manabu Aoki, Robert Shafer, Hiroaki Mitsuya
  • Organizer: 第24回エイズ学会総会グランドプリンスホテル高輪・プリンスさくらタワー東京
  • Place of Presentation: 東京
• [Presentation] HIVプロテアーゼ阻害能(PI)とプロテアーゼ2量体形成阻害能(PDI)を有する新規化合物の同定と野生株・多剤耐性株に対する抗ウイルス活性の検討 (2010)
  • Author(s): 井手一彦、青木学、天野将之、〓康博、Arun K.Ghosh、満屋裕明
  • Organizer: 第24回エイズ学会総会 グランドプリンスホテル高輪・プリンスさくらタワー東京
  • Place of Presentation: 東京
• [Presentation] HIV-1の体内播種とin vivo imaging-概要- (2010)
  • Author(s): 鍬田伸好、青木宏美、服部真一朗、中村太平、青木学、前田賢次、岡田誠治、満屋裕明
  • Organizer: 第24回エイズ学会総会グランドプリンスホテル高輪・プリンスさくらタワー東京
  • Place of Presentation: 東京
• [Presentation] HIV-1の体内播種とin vivo imaging-詳細- (2010)
  • Author(s): 青木宏美、鍬田伸好、服部真一朗、中村太平、青木学、前田賢次、岡田誠治、満屋裕明
  • Organizer: 第24回エイズ学会総会 グランドプリンスホテル高輪・プリンスさくらタワー東京
  • Place of Presentation: 東京
• [Presentation] Tipranavir耐性HIVはプロテアーゼ二量体化阻止能と酵素活性阻止能の双方を喪失している (2010)
  • Author(s): 青木学、井手一彦、Matthew L.Danish、満屋裕明
  • Organizer: 第24回エイズ学会総会 グランドプリンスホテル高輪・プリンスさくらタワー東京
  • Place of Presentation: 東京
• [Presentation] HIV-1 capsid蛋白(CA)の挿入変異とCA自壊の分子機構の解明 (2010)
  • Author(s): 天野将之、田宮貞宏、〓康博、Matthew Danish、満屋裕明
  • Organizer: 第24回エイズ学会総会グランドプリンスホテル高輪・プリンスさくらタワー東京
  • Place of Presentation: 東京
• [Presentation] 播種性ヒストプラズマ症と脳原発リンパ腫にて発症した1例 (2010)
  • Author(s): 宮川寿一、徳永賢治、川口辰哉、満屋裕明
  • Organizer: 第24回エイズ学会総会グランドプリンスホテル高輪・プリンスさくらタワー東京
  • Place of Presentation: 東京
• [Presentation] Novel HIV-1 protease inhibitors (PIs) containing bis-tetrahydrofuran (bis- THF) and a novel polycyclic ligand (2010)
  • Author(s): Kazuhiko Ide, Manabu Aoki, Yasuhiro Koh, Masayuki Amano, Sarang Kulkarni, David D. Anderson, Bruno Chapsal, Arun K. Ghosh, Hiroaki Mitsuya
  • Organizer: XVIII International AIDS conference
  • Place of Presentation: The Reed Messe Wien, Vienna,Austria, No. MOAA0102.
• [Presentation] The Binary Protease Inhibitor, Darunavir, Has a High Genetic Barrier to the Emergence of Resistant HIV-1 Variants (2010)
  • Author(s): Yasuhiro Koh, M Aoki, M,Amano, H Ogata-Aoki, S Leschenko-Yashchuk, A Ghosh, H Mitsuya
  • Organizer: 17th Conference on Retroviruses and Opportunistic Infections.No.p559.
  • Place of Presentation: Moscone Center West, San Francisco, CA, USA
• [Presentation] HIV-1 capsid蛋白(CA)の挿入変異とCA自壊の分子機構の解明 (2010)
  • Author(s): 天野将之
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪・プリンスさくらタワー東京
• [Presentation] Mechanism of the Emergence of HIV-1 Variants Highly Resistaut to Darunavir (2010)
  • Author(s): Matthew L.Danish
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪・プリンスさくらタワー東京
• [Presentation] mCherry可視化HIV-1を用いたHIV-1体内播種早期ダイナミクスの検討:1 (2010)
  • Author(s): 鍬田伸好
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪・プリンスさくらタワー東京
• [Presentation] mCherry可視化HIV-1を用いたHIV-1体内播種早期ダイナミクスの検討:2 (2010)
  • Author(s): 青木宏美
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪・プリンスさくらタワー東京
• [Presentation] HIVプロテアーゼ阻害能(PI)とプロテアーゼ2量体形成阻害能(PDI)を有する新規化合物の同定と野生株・多剤耐性株に対する抗ウイルス活性の検討 (2010)
  • Author(s): 井手一彦
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪・プリンスさくらタワー東京
• [Presentation] Tipranavir而性HIVはプロテアーゼニ量体化阻止能と酵素活性阻止能の双方を喪失している (2010)
  • Author(s): 青木学
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪・プリンスさくらタワー東京
• [Presentation] 播種性ヒストプラズマ症と脳原発リンパ腫にて発症した1例 (2010)
  • Author(s): 宮川寿一
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪・プリンスさくらタワー東京
• [Presentation] HIVプロテアーゼ阻害(PI)とプロテアーゼ2量体形成阻害(PDI)の2活性を有する新規化合物の同定と抗HIV活性の検討 (2009)
  • Author(s): 井手一彦、〓康博、天野将之、Arun K.Ghosh、満屋裕明
  • Organizer: 第23回エイズ学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] Macrocyclic構造を有する新規プロテアーゼ阻害剤の抗HIV-1活性の検討 (2009)
  • Author(s): 東條靖、〓康博、天野将之、Arun K, Ghosh、満屋裕明
  • Organizer: 第23回エイズ学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] HIV-1の体内播種とin vivo imaging-1 (2009)
  • Author(s): 鍬田伸好、青木宏美、服部真一朗、中村太平、青木学、前田賢次、岡田誠治、満屋裕明
  • Organizer: 第23回エイズ学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] HIV-1の体内播種とin vivo imaging-2 (2009)
  • Author(s): 青木宏美、鍬田伸好、服部真一朗、中村太平、青木学、前田賢次、岡田誠治、満屋裕明
  • Organizer: 第23回エイズ学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] 感染細胞内でHIVコンポーネントの自壊をもたらす機序の解明 (2009)
  • Author(s): 天野将之、〓康博、田宮貞弘、満屋裕明
  • Organizer: 第23回エイズ学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] ドミノ肝移植にて救命し得たHIV・HCV 重複感染肝不全症例 (2009)
  • Author(s): 宮川寿一、満屋裕明、山本栄和、猪俣裕紀洋、松下修三、塚田訓久、岡慎一
  • Organizer: 第23回エイズ学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] The binary mechanism of HIV-1 resistance to tipranavir (TPV) : Loss of inhibition of protease catalytic activity and protease dimerization (2009)
  • Author(s): Manabu Aoki, Yasuhiro Koh, Kazuhiko Ide, Matthew L. Danish, Hiromi Aoki-Ogata, Hiroaki Mitsuya
  • Organizer: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
  • Place of Presentation: The Moscone Center, San Francisco, CA, USA.
• [Presentation] Degradation of Gag Proteins in Multi -drug-resistant HIV Variants Containing Insertions in Gag Proteins (2009)
  • Author(s): 天野将之, 〓康博, 田宮貞弘, 満屋裕明
  • Organizer: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
  • Place of Presentation: The Moscone Center, San Francisco,CA, USA.
• [Presentation] Macrocyclic Component-containing Protease Inhibitors (PIs) Active Against Multi-PI-Resistant HIV-1 In Vitro (2009)
  • Author(s): Yasushi Tojo, Yasuhiro Koh, Debananda Das, Masayuki Amano, Sarang Kulkarni, David Anderson, Arun K. Ghosh, Hiroaki Mitsuya
  • Organizer: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
  • Place of Presentation: The Moscone Center, San Francisco, CA, USA.
• [Presentation] The binary mechanism of HIV-1 resistance to tipranavir(TPV) : Loss of inhibition of protease catalytic activity and protease dimerization (2009)
  • Author(s): Aokl M, Mitsuya, H., et al.
  • Organizer: 49^<th> Annual Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC)
  • Place of Presentation: San Francisco, CA, US(米国)
• [Presentation] Degradation of Gag Proteins in Multi -drug-resistant HIV Variants Containing Insertions in Gag Proteins (2009)
  • Author(s): Amano M, Mitsuya, H., et al.
  • Organizer: 49^<th> Annual Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC)
  • Place of Presentation: San Francisco, CA, US(米国)
• [Presentation] Macrocyclic Component-containing Protease Inhibitors(PIs)Active Against Multi-PI-Resistant HIV-1 In Vitro (2009)
  • Author(s): Tojo Y, Mitsuya, H., et al.
  • Organizer: 49^<th> Annual Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC)
  • Place of Presentation: San Francisco, CA, US(米国)
• [Presentation] HIV Infection and AIDS : Halt the further spread. (2008)
  • Author(s): Mitsuya, H.
  • Organizer: the 13th Congress of the Asia Pacific League of Associations for Rheumatology, Symposium on Infectious Risk in Developing Countries
  • Place of Presentation: 横浜
  • Year and Date: 2008-11-26
• [Presentation] Development of Antiviral Therapy of HIV Infection : From AZT to Darunavir. (2008)
  • Author(s): Mitsuya, H.
  • Organizer: American Chemical Society 236th National Meeting, Robertson and Scarborough Awards Symposium
  • Place of Presentation: Philadelphia, U.S.A.
  • Year and Date: 2008-08-18
• [Presentation] Anti-HIV Drugs : Past, Present, and Medicinal Challenges. (2008)
  • Author(s): Mitsuya, H.
  • Organizer: American Chemical Society 236th National Meeting, Symposium Honoring Victor Marquez for His Contributions to Conformational Analysis, Nucleosides, Nucleotides and Oligonucleotides
  • Place of Presentation: Philadelphia, U.S.A.
  • Year and Date: 2008-08-18
• [Presentation] Structure-based Development of Antiviral Therapeutics for HIV-1 Infection and AIDS. (2008)
  • Author(s): Mitsuya, H.
  • Organizer: International Conference on Drug Design and Discovery for Developing Countries
  • Place of Presentation: Trieste, Italy