{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:23:07Z","timestamp":1773271387092,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The ongoing global COVID-19 pandemic is caused by SARS-CoV-2, a novel coronavirus first discovered at the end of 2019. It has led to more than 50 million confirmed cases and more than 1 million deaths across 219 countries as of 11 November 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are similar. They are highly pathogenic and threaten public health, impair the economy, and inflict long-term impacts on society. No drug or vaccine has been approved as a treatment for these viruses. Efforts to develop antiviral measures have been hampered by the insufficient understanding of how the human body responds to viral infections at the cellular and molecular levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, journal articles and transcriptomic and proteomic data surveying coronavirus infections were collected. Response genes and proteins were then identified by differential analyses comparing gene\/protein levels between infected and control samples. Finally, the H2V database was created to contain the human genes and proteins that respond to SARS-CoV-2, SARS-CoV, and MERS-CoV infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      H2V provides molecular information about the human response to infection. It can be a powerful tool to discover cellular pathways and processes relevant for viral pathogenesis to identify potential drug targets. It is expected to accelerate the process of antiviral agent development and to inform preparations for potential future coronavirus-related emergencies. The database is available at:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.zhounan.org\/h2v\">http:\/\/www.zhounan.org\/h2v<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12859-020-03935-2","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T12:03:50Z","timestamp":1610021030000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["H2V: a database of human genes and proteins that respond to SARS-CoV-2, SARS-CoV, and MERS-CoV infection"],"prefix":"10.1186","volume":"22","author":[{"given":"Nan","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinku","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuping","family":"Ning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"3935_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1128\/MMBR.69.4.635-664.2005","volume":"69","author":"SR Weiss","year":"2005","unstructured":"Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev. 2005;69:635\u201364. https:\/\/doi.org\/10.1128\/MMBR.69.4.635-664.2005.","journal-title":"Microbiol Mol Biol Rev"},{"key":"3935_CR2","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","volume":"382","author":"N Zhu","year":"2020","unstructured":"Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727\u201333. https:\/\/doi.org\/10.1056\/NEJMoa2001017.","journal-title":"N Engl J Med"},{"key":"3935_CR3","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1001\/jama.2020.2565","volume":"323","author":"Y Bai","year":"2020","unstructured":"Bai Y, Yao L, Wei T, Tian F, Jin D-Y, Chen L, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020;323:1406\u20137. https:\/\/doi.org\/10.1001\/jama.2020.2565.","journal-title":"JAMA"},{"key":"3935_CR4","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jfma.2013.11.006","volume":"113","author":"N Zhou","year":"2014","unstructured":"Zhou N, Zhang Y, Zhang J-C, Feng L, Bao J-K. The receptor binding domain of MERS-CoV: the dawn of vaccine and treatment development. J Formos Med Assoc. 2014;113:143\u20137. https:\/\/doi.org\/10.1016\/j.jfma.2013.11.006.","journal-title":"J Formos Med Assoc"},{"issue":"281\u2013292","key":"3935_CR5","doi-asserted-by":"publisher","first-page":"e6","DOI":"10.1016\/j.cell.2020.02.058","volume":"181","author":"AC Walls","year":"2020","unstructured":"Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181(281\u2013292):e6. https:\/\/doi.org\/10.1016\/j.cell.2020.02.058.","journal-title":"Cell"},{"key":"3935_CR6","doi-asserted-by":"publisher","first-page":"e30","DOI":"10.1093\/gerona\/glaa094","volume":"75","author":"DEL Promislow","year":"2020","unstructured":"Promislow DEL. A Geroscience perspective on COVID-19 mortality. J Gerontol Ser A. 2020;75:e30\u20133. https:\/\/doi.org\/10.1093\/gerona\/glaa094.","journal-title":"J Gerontol Ser A"},{"key":"3935_CR7","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S1473-3099(20)30243-7","volume":"20","author":"R Verity","year":"2020","unstructured":"Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20:669\u201377. https:\/\/doi.org\/10.1016\/S1473-3099(20)30243-7.","journal-title":"Lancet Infect Dis"},{"key":"3935_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/B978-0-12-809633-8.21501-X","volume":"1","author":"DX Liu","year":"2020","unstructured":"Liu DX, Liang JQ, Fung TS. Human coronavirus-229E, -OC43, -NL63, and -HKU1. Ref Modul Life Sci. 2020;1:1. https:\/\/doi.org\/10.1016\/B978-0-12-809633-8.21501-X.","journal-title":"Ref Modul Life Sci"},{"key":"3935_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.035","author":"L Dai","year":"2020","unstructured":"Dai L, Zheng T, Xu K, Han Y, Xu L, Huang E, et al. A universal design of betacoronavirus vaccines against COVID-19, MERS, and SARS. Cell. 2020. https:\/\/doi.org\/10.1016\/j.cell.2020.06.035.","journal-title":"Cell"},{"key":"3935_CR10","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270\u20133. https:\/\/doi.org\/10.1038\/s41586-020-2012-7.","journal-title":"Nature"},{"key":"3935_CR11","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine-Weber H, Schroeder S, Kr\u00fcger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-280.e8. https:\/\/doi.org\/10.1016\/j.cell.2020.02.052.","journal-title":"Cell"},{"key":"3935_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/2020.06.17.156455","volume":"1","author":"A Stukalov","year":"2020","unstructured":"Stukalov A, Girault V, Grass V, Bergant V, Karayel O, Urban C, et al. Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV. bioRxiv. 2020;1:1. https:\/\/doi.org\/10.1101\/2020.06.17.156455.","journal-title":"bioRxiv"},{"key":"3935_CR13","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1126\/science.abc1669","volume":"369","author":"MM Lamers","year":"2020","unstructured":"Lamers MM, Beumer J, van der Vaart J, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020;369:50\u20134. https:\/\/doi.org\/10.1126\/science.abc1669.","journal-title":"Science"},{"key":"3935_CR14","doi-asserted-by":"publisher","first-page":"e8729","DOI":"10.1371\/journal.pone.0008729","volume":"5","author":"T Yoshikawa","year":"2010","unstructured":"Yoshikawa T, Hill TE, Yoshikawa N, Popov VL, Galindo CL, Garner HR, et al. Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection. PLoS ONE. 2010;5:e8729. https:\/\/doi.org\/10.1371\/journal.pone.0008729.","journal-title":"PLoS ONE"},{"key":"3935_CR15","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1074\/mcp.M400112-MCP200","volume":"4","author":"X-S Jiang","year":"2005","unstructured":"Jiang X-S, Tang L-Y, Dai J, Zhou H, Li S-J, Xia Q-C, et al. Quantitative analysis of severe acute respiratory syndrome (SARS)-associated coronavirus-infected cells using proteomic approaches. Mol Cell Proteomics. 2005;4:902\u201313. https:\/\/doi.org\/10.1074\/mcp.M400112-MCP200.","journal-title":"Mol Cell Proteomics"},{"key":"3935_CR16","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1080\/22221751.2020.1738277","volume":"9","author":"X Zhang","year":"2020","unstructured":"Zhang X, Chu H, Wen L, Shuai H, Yang D, Wang Y, et al. Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation. Emerg Microbes Infect. 2020;9:733\u201346. https:\/\/doi.org\/10.1080\/22221751.2020.1738277.","journal-title":"Emerg Microbes Infect"},{"key":"3935_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2286-9","author":"DE Gordon","year":"2020","unstructured":"Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020. https:\/\/doi.org\/10.1038\/s41586-020-2286-9.","journal-title":"Nature"},{"key":"3935_CR18","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe9403","author":"DE Gordon","year":"2020","unstructured":"Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, et al. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science. 2020. https:\/\/doi.org\/10.1126\/science.abe9403.","journal-title":"Science"},{"key":"3935_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2332-7","author":"D Bojkova","year":"2020","unstructured":"Bojkova D, Klann K, Koch B, Widera M, Krause D, Ciesek S, et al. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature. 2020. https:\/\/doi.org\/10.1038\/s41586-020-2332-7.","journal-title":"Nature"},{"key":"3935_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.034","author":"M Bouhaddou","year":"2020","unstructured":"Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Marrero MC, et al. The global phosphorylation landscape of SARS-CoV-2 infection. Cell. 2020. https:\/\/doi.org\/10.1016\/j.cell.2020.06.034.","journal-title":"Cell"},{"issue":"164\u2013174","key":"3935_CR21","doi-asserted-by":"publisher","first-page":"e4","DOI":"10.1016\/j.molcel.2020.08.006","volume":"80","author":"K Klann","year":"2020","unstructured":"Klann K, Bojkova D, Tascher G, Ciesek S, M\u00fcnch C, Cinatl J. Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication. Mol Cell. 2020;80(164\u2013174):e4. https:\/\/doi.org\/10.1016\/j.molcel.2020.08.006.","journal-title":"Mol Cell"},{"key":"3935_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.032","author":"B Shen","year":"2020","unstructured":"Shen B, Yi X, Sun Y, Bi X, Du J, Zhang C, et al. Proteomic and metabolomic characterization of COVID-19 patient sera. Cell. 2020. https:\/\/doi.org\/10.1016\/j.cell.2020.05.032.","journal-title":"Cell"},{"key":"3935_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/2020.05.02.20088666","volume":"1","author":"Y Li","year":"2020","unstructured":"Li Y, Wang Y, Liu H, Sun W, Ding B, Zhao Y, et al. Urine proteome of COVID-19 patients. medRxiv. 2020;1:1. https:\/\/doi.org\/10.1101\/2020.05.02.20088666.","journal-title":"medRxiv"},{"key":"3935_CR24","doi-asserted-by":"publisher","first-page":"e69374","DOI":"10.1371\/journal.pone.0069374","volume":"8","author":"HD Mitchell","year":"2013","unstructured":"Mitchell HD, Eisfeld AJ, Sims AC, McDermott JE, Matzke MM, Webb-Robertson B-JM, et al. A network integration approach to predict conserved regulators related to pathogenicity of influenza and SARS-CoV respiratory viruses. PLoS ONE. 2013;8:e69374. https:\/\/doi.org\/10.1371\/journal.pone.0069374.","journal-title":"PLoS ONE"},{"key":"3935_CR25","doi-asserted-by":"publisher","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","volume":"46","author":"DS Wishart","year":"2017","unstructured":"Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017;46:D1074\u201382. https:\/\/doi.org\/10.1093\/nar\/gkx1037.","journal-title":"Nucleic Acids Res"},{"key":"3935_CR26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/bioinformatics\/btv557","volume":"32","author":"M Franz","year":"2015","unstructured":"Franz M, Lopes CT, Huck G, Dong Y, Sumer O, Bader GD. Cytoscape. js: a graph theory library for visualisation and analysis. Bioinformatics. 2015;32:309\u201311.","journal-title":"Bioinformatics"},{"key":"3935_CR27","doi-asserted-by":"publisher","first-page":"D419","DOI":"10.1093\/nar\/gky1038","volume":"47","author":"H Mi","year":"2019","unstructured":"Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2019;47:D419\u201326. https:\/\/doi.org\/10.1093\/nar\/gky1038.","journal-title":"Nucleic Acids Res"},{"key":"3935_CR28","doi-asserted-by":"publisher","first-page":"D506","DOI":"10.1093\/nar\/gky1049","volume":"47","author":"Consortium TU","year":"2018","unstructured":"Consortium TU. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2018;47:D506\u201315. https:\/\/doi.org\/10.1093\/nar\/gky1049.","journal-title":"Nucleic Acids Res"},{"key":"3935_CR29","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baaa021","author":"N Zhou","year":"2020","unstructured":"Zhou N, Bao J. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database (Oxford). 2020. https:\/\/doi.org\/10.1093\/database\/baaa021.","journal-title":"Database (Oxford)"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-03935-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-020-03935-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-03935-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T01:04:07Z","timestamp":1697504647000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-020-03935-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,7]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3935"],"URL":"https:\/\/doi.org\/10.1186\/s12859-020-03935-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-61338\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-61338\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-61338\/v3","asserted-by":"object"}]},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,7]]},"assertion":[{"value":"5 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18"}}