Yuichiro Hara, Haruki Kitamura, Kouki Matsuda, Sayaka Sukegawa, Kosuke Tanimoto, Chieko Fujisaki, Kenji Maeda, Hiroaki Takeuchi . Identification of a novel small molecule facilitating HIV elim2025 · 出版者・発行元： openRxiv Abstract The development of antiretroviral therapy (ART) has significantly improved the prognosis of people living with HIV (PLWH). However, reservoirs of latent viruses represent a major barrier to achieving a complete cure of HIV infection. To overcome the burden of viral latency, the “Shock-and-Kill” strategy employs latency-reversing agents (LRAs) to reactivate the virus and thus render it susceptible to elimination. Existing LRAs are not optimal and there is an unmet need for improvement. By screening a small molecule library, we identified the novel LRA candidate 2-HSB (2-hydrido-2,2’-spirobi(1,3,2-benzodioxaphosphole)) which not only reactivates latent HIV provirus but also induces specific cytopathic effects in both monocytic and T lymphocytic latent HIV reservoirs. Thus, this novel compound represents a dual “shock and kill” agent, unlike known LRAs which are limited to the “shock”. The probable involvement of HIV-1 tat protein may account for its selectivity. Although both shock and kill effects seemed to be regulated by spleen tyrosine kinase, they were independent of each other, indicating that neither activation-induced cell death nor cell death-induced reactivation was occurring. Crucially, 2-HSB induced viral transcription in ART-suppressed PLWH samples in vitro. Our findings present 2-HSB as a promising dual-action compound for the “Shock and Kill” strategy, demonstrating efficacy in both transformed cell lines and clinically-relevant primary samples. These results raise the possibility of distinguishing the mode of action of the two effects, potentially leading to the development of a single agent causing both HIV-1 reactivation and elimination and contributing to the improvement of treatment. DOI： 10.64898/2025.12.03.692014 researchmap
Yamamoto S., Matsuda K., Maeda K., Horii K., Okudera K., Oshiro Y., Inamura N., Takeuchi J.S., Konishi M., Ozeki M., Mizoue T., Sugiyama H., Aoyanagi N., Mitsuya H., Sugiura W., Ohmagari N. .2023 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： International Journal of Infectious Diseases Objectives: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection. Methods: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19. Among these cases, we examined the association between NAb levels and the number of COVID-19-compatible symptoms. Results: Among the 1456 participants for VE analysis, 60 breakthrough infections occurred during the Omicron wave. The third dose VE for infection was 54.6%. Among the third dose recipients, NAb levels against Omicron did not differ between the cases (n = 22) and controls (n = 21). Among the cases, those who experienced COVID-19-compatible symptoms had lower NAb levels against Omicron than those who did not. Conclusion: The third vaccine dose was effective in decreasing the risk of SARS-CoV-2 infection during Omicron wave compared with the second dose. Among third dose recipients, higher preinfection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection. DOI： 10.1016/j.ijid.2023.01.023 Scopus PubMed researchmap
