Development of the novel HIV eradication method

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23802
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Tateishi Hiroshi 熊本大学, 大学院生命科学研究部(薬), 特任助教 (50846011)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: HIV / Gag蛋白質 / MAドメイン / L-HIPPO / Lock-in and apoptosis

Outline of Final Research Achievements

In this study, we aimed to eradicate latently infected cells using the Lock-in and apoptosis method, and investigated the binding form of L-HIPPO and MA domain, and synthesis of prodrug derivative.
First, in order to check the binding form, about 600 types of crystallization conditions were examined by the vapor diffusion method. Although crystals were obtained, no L-HIPPO binding was observed. Currently, due to carry out crystallization by the lipid cubic phase method, purification of myristoylated MA protein (Myr-MA) and Myr-Gag has been started and obtained high-purity protein. On the other hand, we synthesized prodrug L-HIPPO and confirmed the virus release inhibitory effect. we succeeded in improving the membrane permeability. Induction of cell death in latently infected cells is currently confirmed.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

多剤併用療法（ART）の導入によりHIV感染症は不治の病からコントロール可能な慢性疾患と捉えられるまでになった。しかしながら、現在の治療法では完治しないため一生薬を飲み続ける必要があり、その結果、副作用や合併症などが見られるようになった。実際に、多施設コホート研究によりHIV 感染者でART 治療群では、非HIV 感染者に比して約4 倍糖尿病の罹患率が高くなるという報告もある。HIVの完治が求められているが、本研究にて開発中であるLock-in and apoptosis法は、HIVの根絶に結びつくものと期待される。