{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T06:09:27Z","timestamp":1778479767527,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Since the emergence and spread of coronavirus disease 2019 (COVID-19), Traditional Chinese Medicine (TCM) and its formulations have been used extensively in China for preventing and treating COVID-19 with demonstrated clinical efficacy. This study aimed to evaluate both the therapeutic potential and the mechanism of action of a newly designed TCM formula, JinHuangJieDu (JHJD), which is composed of\n                      <jats:italic>Lonicerae Japonicae Flos<\/jats:italic>\n                      ,\n                      <jats:italic>Scutellariae Radix, Pogostemonis Herba<\/jats:italic>\n                      ,\n                      <jats:italic>Angelicae Dahuricae Radix<\/jats:italic>\n                      ,\n                      <jats:italic>Taraxaci Herba<\/jats:italic>\n                      , and\n                      <jats:italic>Menthae Haplocalycis Herba<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The inhibitory effects of JHJD on SARS-CoV-2 spike RBD binding to ACE2 and pseudovirus infection were assessed\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Network pharmacology analyses predicted JHJD\u2019s active ingredients, target genes, and enriched pathways. Key targets were validated in vitro for their role in mitigating virus-induced inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      JHJD effectively blocked wildtype and Omicron RBD binding to ACE2 and inhibited pseudovirus infection. Network analyses identified 375 ingredients, 338 targets (primarily in lung, stomach and spleen), and 63 significant pathways related to viral infection\/inflammation. Intersectional analysis suggested\n                      <jats:italic>CCND1<\/jats:italic>\n                      and\n                      <jats:italic>HIF1A<\/jats:italic>\n                      as pivotal genes and\n                      <jats:italic>in vitr<\/jats:italic>\n                      o validation confirmed that JHJD targets HIF-1\u03b1 to attenuate inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>JHJD, a de novo designed TCM formula, effectively inhibits SARS-CoV-2 entry with superior efficacy against Omicron sub-variants. The formulation has a dual mode of action including disruption of the RBD\u2013ACE2 interaction and alleviation of virus-induced inflammation by modulating HIF-1\u03b1. These dual mechanisms establish JHJD as a promising therapeutic candidate for COVID-19.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1817137","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:30:02Z","timestamp":1778477402000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["JinHuangJieDu (JHJD) formula attenuates SARS-CoV-2 infection by interrupting RBD-ACE2 binding and HIF-1\u03b1-dependent inflammation"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhan-Qun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Peking University Third Hospital Cancer Center, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Institute of Advanced Clinical Medicine, Peking University","place":["Beijing, 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