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Shufeng Jiedu formula (SFJD), a traditional Chinese remedy, is used for treating RTI, though its mechanisms are not well understood. The objective of this research was to uncover the underlying molecular mechanisms responsible for the effectiveness of SFJD on RTI. Using UHPLC-Q-Orbitrap HRMS assays, the chemical compounds in SFJD\u2019s ethanol and aqueous extracts fractions were identified. The targets of these herbal compounds and RTI-related targets were acquired from various database. Key SFJD-RTI targets were analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and tissue\/organ-specific analyses. Molecular docking, data mining and dynamic simulations were employed to evaluate interactions between major targets and the main compounds. A total of 94 and 31 compounds were determined in the aqueous and ethanol extract fraction, respectively. Many of these compounds demonstrated good oral bio-availability (60\/99). GO analysis revealed significant involvement in inflammatory response and gene silencing processes, while KEGG pathways highlighted connections to viral infections and signaling pathways. The lung was the primary target organ screed out by Biogps databases and 15 compounds as well as eight key genes were associated. A set of 15 compounds were virtually fitted into the active site of eight critical targets. Isaindigotone and resveratrol could form hydrogen bond interactions with FOS and JUN, respectively. FOS and JUN were classified as differential genes after the COVID-2019, HCoV-229E and H1N1 infected. The comprehensive results obtained from MD simulation, MMPBSA, and SASA analysis highlighted the compounds\u2019 potential to serve as effective inhibitors of FOS and JUN proteins. Lastly, resveratrol exerted a high inhibitory effect on the influenza virus based on MDCK cells. In summary, we have provided a framework that integrated network pharmacology with multiple virus infection models to identify synergistic compounds based on network topology.<\/jats:p>","DOI":"10.1093\/bib\/bbaf353","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T22:44:19Z","timestamp":1755038659000},"source":"Crossref","is-referenced-by-count":0,"title":["An advanced network pharmacology investigation of Shufeng Jiedu formula in the treatment for respiratory tract infection based on LC\u2013MS, data mining, molecular docking, and molecular dynamic simulation"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1070-4960","authenticated-orcid":false,"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Huijun","family":"Wang","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Chaochao","family":"Wang","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Xiaolan","family":"Cui","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Shanshan","family":"Guo","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Junyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Lihua","family":"Chen","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Xiaolu","family":"Wei","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica , No. 16, Dongzhimen Nei Nanxiao Street, Dongcheng District, Beijing 100700 ,","place":["China"]}]},{"given":"Haiyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences, Institute of Chinese 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