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The \u201cShock and Kill\u201d strategy aims to reactivate latent provirus with latency\u2010reversing agents (LRAs) and subsequently eliminate the infected cells, yet most LRAs characterized to date provide only the \u201cshock\u201d component. Through screening a small\u2010molecule library, we identified 2\u2010hydrido\u20102,2'\u2010spirobi(1,3,2\u2010benzodioxaphosphole) (2\u2010HSB) as a novel candidate that both reactivates latent HIV provirus and selectively induces cytopathic effects in latently infected reservoir cell lines, thereby exhibiting a dual \u201cShock and Kill\u201d activity within a single compound. Mechanistically, the HIV\u20101\n                    <jats:italic>tat<\/jats:italic>\n                    protein appears to contribute to this selectivity. At the single\u2010cell level, the two effects appeared largely independent, indicating that, under the conditions tested, reactivation was not a consequence of cell death and vice versa. Importantly, 2\u2010HSB induced viral transcription in ex vivo CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from ART\u2010suppressed PLWH. Together, these findings identify 2\u2010HSB as a dual\u2010action candidate that reactivates latent HIV\u20101 and preferentially induces cytopathic effects in reservoir cell\u2010line models, while supporting further mechanistic and ex vivo validation in primary reservoir\u2010bearing cells.\n                  <\/jats:p>","DOI":"10.1002\/jmv.71131","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T19:06:20Z","timestamp":1788203180000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Novel Small Molecule Facilitating HIV Elimination by the \u201cShock\u2010And\u2010Kill\u201d Approach"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6825-9627","authenticated-orcid":false,"given":"Yuichiro","family":"Hara","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine Institute of Science Tokyo Tokyo 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