{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:12:26Z","timestamp":1776921146594,"version":"3.51.2"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T00:00:00Z","timestamp":1595203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002467","name":"Dankook University","doi-asserted-by":"publisher","award":["The present research was conducted by the research fund of Dankook University in 2020."],"award-info":[{"award-number":["The present research was conducted by the research fund of Dankook University in 2020."]}],"id":[{"id":"10.13039\/501100002467","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects almost everyone in the world in many ways. We previously predicted antivirals (atazanavir, remdesivir and lopinavir\/ritonavir) and non-antiviral drugs (tiotropium and rapamycin) that may inhibit the replication complex of SARS-CoV-2 using our molecular transformer\u2013drug target interaction (MT\u2013DTI) deep-learning-based drug\u2013target affinity prediction model. In this study, we dissected molecular pathways upregulated in SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells by analyzing an RNA-seq data set with various bioinformatics approaches, such as gene ontology, protein\u2013protein interaction-based network and gene set enrichment analyses. The results indicated that the SARS-CoV-2 infection strongly activates TNF and NF\u03baB-signaling pathways through significant upregulation of the TNF, IL1B, IL6, IL8, NFKB1, NFKB2 and RELB genes. In addition to these pathways, lung fibrosis, keratinization\/cornification, rheumatoid arthritis, and negative regulation of interferon-gamma production pathways were also significantly upregulated. We observed that these pathologic features of SARS-CoV-2 are similar to those observed in patients with chronic obstructive pulmonary disease (COPD). Intriguingly, tiotropium, as predicted by MT\u2013DTI, is currently used as a therapeutic intervention in COPD patients. Treatment with tiotropium has been shown to improve pulmonary function by alleviating airway inflammation. Accordingly, a literature search summarized that tiotropium reduced expressions of IL1B, IL6, IL8, RELA, NFKB1 and TNF in vitro or in vivo, and many of them have been known to be deregulated in COPD patients. These results suggest that COVID-19 is similar to an acute mode of COPD caused by the SARS-CoV-2 infection, and therefore tiotropium may be effective for COVID-19 patients.<\/jats:p>","DOI":"10.3390\/v12070776","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T10:59:38Z","timestamp":1595242778000},"page":"776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Tiotropium Is Predicted to Be a Promising Drug for COVID-19 Through Transcriptome-Based Comprehensive Molecular Pathway Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Keunsoo","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Microbiology, College of Science &amp; Technology, Dankook University, Cheonan 31116, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Science &amp; Technology, Dankook University, Cheonan 31116, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoonjung","family":"Choi","sequence":"additional","affiliation":[{"name":"Deargen Inc., Daejeon, Yuseong-gu, Munji-dong 103-6, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3201\/eid1209.05-0979","article-title":"Influenza: The mother of all pandemics","volume":"12","author":"Taubenberger","year":"2006","journal-title":"Emerg. 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