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Therefore, interference with virus movement represents an attractive antiviral strategy. Here, we report a series of perillaldehyde\u2010derived compounds bearing an\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \u2010aminophosphonate moiety, evaluate their anti\u2010phytoviral activities, and elucidate the mechanism of a representative lead.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 38 target derivatives were designed and synthesized by introducing an aminophosphonate pharmacophore onto the perillaldehyde scaffold. Using the half\u2010leaf lesion assay, compound\n                      <jats:bold>Y14<\/jats:bold>\n                      was identified as a potent inhibitor against\n                      <jats:italic>Potato virus Y<\/jats:italic>\n                      (PVY), exhibiting an inactivation half\u2010maximal effective concentration (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) of 122.40\u2009\u00b1\u20099.34\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      , outperforming the commercial antiviral dufulin (140.40\u2009\u00b1\u20096.75\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) and ribavirin (238.90\u2009\u00b1\u200910.58\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Activity\u2010based protein profiling, molecular docking, microscale thermophoresis, together with immunoblotting and real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR) analyses, collectively suggested that Ser207 in the PVY coat protein (CP) is a key residue for compound\n                      <jats:bold>Y14<\/jats:bold>\n                      engagement. Notably, the CP\n                      <jats:sup>S207A<\/jats:sup>\n                      mutation markedly reduced the binding affinity of compound\n                      <jats:bold>Y14<\/jats:bold>\n                      and attenuated PVY systemic infection in planta. Confocal imaging showed that the CP\n                      <jats:sup>S207A<\/jats:sup>\n                      recombinant PVY produced predominantly single\u2010cell fluorescence, indicating impaired cell\u2010to\u2010cell movement. The co\u2010immunoprecipitation results further suggested that this inhibition may arise from disrupted interaction with the host factor NtCPIP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      This study identifies compound\n                      <jats:bold>Y14<\/jats:bold>\n                      as an antiviral lead that targets PVY CP and functionally compromises viral intercellular spread, thereby suppressing systemic infection. These findings provide a mechanistically distinctive chemical for PVY management. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ps.70818","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T03:51:07Z","timestamp":1776397867000},"page":"7549-7563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A perillaldehyde\u2010derived virucide targets phytoviral coat protein at Ser207 to impede intercellular spread"],"prefix":"10.1002","volume":"82","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Green Pesticide Center for R&amp;D of Fine Chemicals of Guizhou University  Guiyang P. R. 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