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Effective treatments have been delayed by substantial gaps in our knowledge of the fundamental virology, especially when compared to the closely related virus, HIV. A recently developed and highly effective anti-HIV strategy is to target the virus with drugs that interfere with capsid integrity and interactions with the host. Importantly, the first in-class anti-capsid drug approved, lenacapavir, can provide long-acting pre-exposure prophylaxis. Such a property would provide a means to prevent the transmission of HTLV-1, but its capsid has not previously been considered as a drug target. Here we describe high-resolution crystal structures of the HTLV-1 capsid protein, define essential lattice interfaces, and identify a distinct ligand-binding pocket. We show that this pocket is essential for virus infectivity, providing a potential target for future anti-capsid drug development.<\/jats:p>","DOI":"10.1038\/s41467-025-65899-2","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T11:20:40Z","timestamp":1764847240000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Human T-cell Leukemia Virus capsid protein is a potential drug target"],"prefix":"10.1038","volume":"16","author":[{"given":"Ruijie","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhjeet","family":"Phalora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-3122","authenticated-orcid":false,"given":"Till","family":"B\u00f6cking","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6426-4510","authenticated-orcid":false,"given":"David Anthony","family":"Jacques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"65899_CR1","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.3389\/fmicb.2017.01425","volume":"8","author":"Y Tagaya","year":"2017","unstructured":"Tagaya, Y. & Gallo, R. 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