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Several natural compounds were selected to screen the inhibitory effect on T\u2010cell proliferation by Fluorescence\u2010Activated Cell Sorting (FACS) and cytokine production by enzyme\u2010linked immunosorbent assay (ELISA). Open reading frame 3a (ORF3a) of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) stimulates the specific T\u2010cell activation model in vivo and in vitro. The coculture system included the macrophage cell line RAW264.7 and splenocytes. Reactive oxygen species (ROS) levels and glycolysis in T cells were evaluated. Cinnamaldehyde effectively inhibits cytokine storms both in vitro and in vivo. It decreased inflammatory cytokine (such as IFN\u2010\u03b3, TNF\u2010\u03b1, IL\u20106, and IL\u20102) production by murine peripheral blood cells upon direct stimulation with ConA, after immunization with the MHV\u2010A59 virus or ORF3a peptide from SARS\u2010CoV\u20102. Cinnamaldehyde restored the percentage of T cells, which was originally decreased in the peripheral blood and splenocytes of ORF3a\u2010immunized mice. In a coculture system, cinnamaldehyde reduced the secretion of inflammatory cytokines from macrophages in a T\u2010cell dependent manner. Furthermore, cinnamaldehyde decreased the ROS level in activated T cells, which in turn reduced glycolysis and the activation of T cells. Cinnamaldehyde can be used as a candidate molecule for COVID\u201019.<\/jats:p>","DOI":"10.1002\/ptr.8016","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T05:54:21Z","timestamp":1695189261000},"page":"6006-6020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cinnamaldehyde inhibits cytokine storms induced by the <scp>ORF3a<\/scp> protein of <scp>SARS\u2010CoV<\/scp>\u20102 via <scp>ROS<\/scp>\u2010elimination in activated T cells"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8882-5186","authenticated-orcid":false,"given":"Jing","family":"Ma","sequence":"first","affiliation":[{"name":"Medical Research Center The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"},{"name":"Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics, Chinese Academy of Sciences  Beijing China"},{"name":"University of 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