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The replication, movement and immune evasion of many plant viruses within their hosts are associated with phase separation (PS)\u2010derived aggregates formed by viral components. However, the host factors that drive the formation of these condensates remain largely unknown. This study provides evidence that the nucleocapsid protein (N) of tomato spotted wilt virus (TSWV) recruits the host factor phosphoglycerate kinase (NbPGK) from\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    to form phase\u2010separated condensates. This remodels the host glycolytic pathway to generate ATP, supplying energy for viral replication via ribonucleoprotein complexes and acting as a promoter to regulate the PS network, thereby facilitating condensate formation. Notably, we have developed a small\u2010molecule PS modulator,\n                    <jats:bold>F10<\/jats:bold>\n                    . By combining drug affinity\u2010responsive target stability, molecular docking, microscale thermophoresis and bio\u2010layer interferometry techniques allowed\n                    <jats:bold>F10<\/jats:bold>\n                    , we confirmed binding to sites Arg94, Lys192 and Gly228 on TSWV N, residues critical for maintaining NbPGK recruitment.\n                    <jats:bold>F10<\/jats:bold>\n                    interacts with N, liberating the hijacked host factor NbPGK, and exhibits potent antiviral activity, outperforming the commercial virucide Ningnanmycin. This study elucidates the molecular machinery underlying viral exploitation of host cellular metabolism and identifies a lead compound that is amenable to managing TSWV by targeting this process.\n                  <\/jats:p>","DOI":"10.1111\/pbi.70529","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:23:42Z","timestamp":1767705822000},"page":"2826-2842","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tomato Spotted Wilt Virus Reprogrammes Host Glycolysis to Facilitate Proliferation by a Phase\u2010Separated Co\u2010Aggregate of Nucleocapsid Protein and Phosphoglycerate Kinase"],"prefix":"10.1111","volume":"24","author":[{"given":"Guangcheng","family":"Zu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Green Pesticide Center for R&amp;D of Fine Chemicals of Guizhou University  Guiyang 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