{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:27:29Z","timestamp":1770334049768,"version":"3.49.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-\u03b1. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.707287","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T13:10:46Z","timestamp":1627477846000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Identification of COVID-19 and Dengue Host Factor Interaction Networks Based on Integrative Bioinformatics Analyses"],"prefix":"10.3389","volume":"12","author":[{"given":"Wenjiang","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaofeng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.12839","article-title":"Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review","volume":"324","author":"Wiersinga","year":"2020","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60572-9","article-title":"Dengue","volume":"385","author":"Guzman","year":"2015","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e2161","DOI":"10.1002\/rmv.2161","article-title":"Covid-19 and Dengue: Double Punches for Dengue-Endemic Countries in Asia","volume":"31","author":"Harapan","year":"2021","journal-title":"Rev Med Virol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1207","article-title":"Potential Antigenic Cross-Reactivity Between SARS-CoV-2 and Dengue Viruses","author":"Lustig","year":"2020","journal-title":"Clin Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e00927","DOI":"10.1016\/j.idcr.2020.e00927","article-title":"Dengue Serology in Indonesian COVID-19 Patients: Coinfection or Serological Overlap","volume":"22","author":"Kembuan","year":"2020","journal-title":"IDCases"},{"key":"B6","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/S1473-3099(20)30158-4","article-title":"Covert COVID-19 and False-Positive Dengue Serology in Singapore, The Lancet","volume":"20","author":"Yan","year":"2020","journal-title":"Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/jtm\/taaa114","article-title":"COVID-19 and Dengue Co-Infection in a Returning Traveller","volume":"27","author":"Epelboin","year":"2020","journal-title":"J Travel Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.31053\/1853.0605.v77.n1.28031","article-title":"Coinfection Between Dengue and Covid-19: Need for Approach in Endemic Zones","volume":"77","author":"Saavedra-Velasco","year":"2020","journal-title":"Rev Fac Cien Med (Cordoba Argentina)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3201\/eid2702.203439","article-title":"Characteristics of Patients Co-Infected With Severe Acute Respiratory Syndrome Coronavirus 2 and Dengue Virus, Buenos Aires, Argentina, March-June 2020","volume":"27","author":"Carosella","year":"2021","journal-title":"Emerg Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26194","article-title":"Dengue and COVID-19, Overlapping Epidemics? 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