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No approved drugs or vaccines currently exist. ZIKV hijacks host lipid homeostasis to facilitate replication, and inhibitors of fatty acid synthesis decrease its production. However, cells obtain lipids from both\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      synthesis and uptake. Neurons, a primary target of ZIKV pathogenesis, have limited capacity for\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      lipid synthesis and rely more on lipid uptake. We previously demonstrated that lipid uptake inhibitors block influenza virus replication, yet their efficacy against ZIKV\u2014particularly in neuronal cells\u2014remains unknown. In the present study, we examined the anti-ZIKV and fatty acid uptake inhibitory activities of lipofermata, a fatty acid transporter protein isoform 2 (FATP2)\u2012specific inhibitor. Lipofermata effectively inhibited ZIKV production in immortalized hepatocyte (imHC) and SH-SY5Y (neuroblastoma) cell lines, with respective half-maximal inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) values of 1.41 and 1.11\u202f\u03bcM with 50% cytotoxic concentration (CC\n                      <jats:sub>50<\/jats:sub>\n                      )\u202fof more than 20.0\u202f\u03bcM. FATP2 mRNA and protein expression was significantly elevated in infected SH-SY5Y cells. ZIKV also significantly increased cellular phosphatidylcholine content. Lipofermata inhibited fatty acid uptake with an IC\n                      <jats:sub>50<\/jats:sub>\n                      of 7.0\u202f\u03bcM and significantly decreased phosphatidylcholine level. In addition, FATP2 knockdown by siRNA significantly decreased FATP2 mRNA and protein expression in SH-SY5Y and decreased ZIKV titer. These findings suggest that lipofermata disrupts ZIKV replication via fatty acid uptake inhibition. Furthermore, lipofermata at 2 \u00b5M markedly diminished caspase 3\/7 and 8 activities, indicating that lipofermata mitigated ZIKV-induced extrinsic apoptosis in SH-SY5Y. Mitigating apoptosis may result in reduced neuropathogenesis. Consequently, FATP2 may serve as a promising target for anti-ZIKV therapies.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Zika virus can infect and cause severe damages to the brain. There is no effective antiviral drug for the treatment of Zika infection. Similar to many viruses, replication of Zika virus requires lipid. We show here that the virus could upregulate the fatty acid transporter FATP2 in neuroblastoma cells, which may increase the lipid supply in the infected cells, and that inhibiting the fatty acid transporter by lipofermata could suppress the viral replication and apoptosis. ZIKV production was also reduced by FATP2 knockdown. These suggest that FATP2 may be a promising target for the development of anti-Zika medication.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02140-25","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:02:29Z","timestamp":1773234149000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Fatty acid transporter protein isoform 2 (FATP2) inhibitor lipofermata inhibits Zika virus replication and blocks fatty acid uptake in SH-SY5Y neuroblastoma cell line"],"prefix":"10.1128","volume":"14","author":[{"given":"Songkran","family":"Thongon","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01znkr924","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University","place":["Bangkok, 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