{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:45:51Z","timestamp":1790401551380,"version":"4.1.0"},"reference-count":238,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81473256"],"award-info":[{"award-number":["No. 81473256"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["No. 2021-1-I2M-028"],"award-info":[{"award-number":["No. 2021-1-I2M-028"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["No. 2020-I2M-2-010"],"award-info":[{"award-number":["No. 2020-I2M-2-010"]}]},{"name":"Opening Foundation of the State Key Laboratory of Bioactive Substance and Function of Natural Medicines","award":["No. GTZK202109"],"award-info":[{"award-number":["No. GTZK202109"]}]},{"name":"Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study","award":["No. BZ0150"],"award-info":[{"award-number":["No. BZ0150"]}]},{"name":"Disciplines Construction Project","award":["No. 201920200802"],"award-info":[{"award-number":["No. 201920200802"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The rapid development in the field of transcriptomics provides remarkable biomedical insights for drug discovery. In this study, a transcriptome signature reversal approach was conducted to identify the agents against influenza A virus (IAV) infection through dissecting gene expression changes in response to disease or compounds\u2019 perturbations. Two compounds, nifurtimox and chrysin, were identified by a modified Kolmogorov\u2013Smirnov test statistic based on the transcriptional signatures from 81 IAV-infected patients and the gene expression profiles of 1309 compounds. Their activities were verified in vitro with half maximal effective concentrations (EC50s) from 9.1 to 19.1 \u03bcM against H1N1 or H3N2. It also suggested that the two compounds interfered with multiple sessions in IAV infection by reversing the expression of 28 IAV informative genes. Through network-based analysis of the 28 reversed IAV informative genes, a strong synergistic effect of the two compounds was revealed, which was confirmed in vitro. By using the transcriptome signature reversion (TSR) on clinical datasets, this study provides an efficient scheme for the discovery of drugs targeting multiple host factors regarding clinical signs and symptoms, which may also confer an opportunity for decelerating drug-resistant variant emergence.<\/jats:p>","DOI":"10.3390\/ijms23042372","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:47:45Z","timestamp":1645476465000},"page":"2372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of Nifurtimox and Chrysin as Anti-Influenza Virus Agents by Clinical Transcriptome Signature Reversion"],"prefix":"10.3390","volume":"23","author":[{"given":"Yijing","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"},{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9828-7905","authenticated-orcid":false,"given":"Shubing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"},{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"},{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"},{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"},{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"ref_1","unstructured":"(2021, January 28). 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