{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:05:07Z","timestamp":1773756307256,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010021","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000}}],"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["460044"],"award-info":[{"award-number":["460044"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003549","name":"OTKA","doi-asserted-by":"crossref","award":["K134357"],"award-info":[{"award-number":["K134357"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003549","name":"OTKA","doi-asserted-by":"crossref","award":["KH129599"],"award-info":[{"award-number":["KH129599"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["EFOP-3.6.1.-16-2016-00004"],"award-info":[{"award-number":["EFOP-3.6.1.-16-2016-00004"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry for Innovation and Technology of Hungary","award":["TUDFO\/47138\/2019-ITM"],"award-info":[{"award-number":["TUDFO\/47138\/2019-ITM"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Comparing SARS-CoV-2 infection-induced gene expression signatures to drug treatment-induced gene expression signatures is a promising bioinformatic tool to repurpose existing drugs against SARS-CoV-2. The general hypothesis of signature-based drug repurposing is that drugs with inverse similarity to a disease signature can reverse disease phenotype and thus be effective against it. However, in the case of viral infection diseases, like SARS-CoV-2, infected cells also activate adaptive, antiviral pathways, so that the relationship between effective drug and disease signature can be more ambiguous. To address this question, we analysed gene expression data from\n                    <jats:italic>in vitro<\/jats:italic>\n                    SARS-CoV-2 infected cell lines, and gene expression signatures of drugs showing anti-SARS-CoV-2 activity. Our extensive functional genomic analysis showed that both infection and treatment with\n                    <jats:italic>in vitro<\/jats:italic>\n                    effective drugs leads to activation of antiviral pathways like NFkB and JAK-STAT. Based on the similarity\u2014and not inverse similarity\u2014between drug and infection-induced gene expression signatures, we were able to predict the\n                    <jats:italic>in vitro<\/jats:italic>\n                    antiviral activity of drugs. We also identified SREBF1\/2, key regulators of lipid metabolising enzymes, as the most activated transcription factors by several\n                    <jats:italic>in vitro<\/jats:italic>\n                    effective antiviral drugs. Using a fluorescently labeled cholesterol sensor, we showed that these drugs decrease the cholesterol levels of plasma-membrane. Supplementing drug-treated cells with cholesterol reversed the\n                    <jats:italic>in vitro<\/jats:italic>\n                    antiviral effect, suggesting the depleting plasma-membrane cholesterol plays a key role in virus inhibitory mechanism. Our results can help to more effectively repurpose approved drugs against SARS-CoV-2, and also highlights key mechanisms behind their antiviral effect.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010021","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T13:33:59Z","timestamp":1649684039000},"page":"e1010021","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Computational drug repurposing against SARS-CoV-2 reveals plasma membrane cholesterol depletion as key factor of antiviral drug activity"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8779-2383","authenticated-orcid":true,"given":"Szilvia","family":"Barsi","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3887-5657","authenticated-orcid":true,"given":"Henrietta","family":"Papp","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-9023","authenticated-orcid":true,"given":"Alberto","family":"Valdeolivas","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6670-3348","authenticated-orcid":true,"given":"D\u00e1niel J.","family":"T\u00f3th","sequence":"additional","affiliation":[]},{"given":"Anett","family":"Kuczmog","sequence":"additional","affiliation":[]},{"given":"M\u00f3nika","family":"Madai","sequence":"additional","affiliation":[]},{"given":"L\u00e1szl\u00f3","family":"Hunyady","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7777-806X","authenticated-orcid":true,"given":"P\u00e9ter","family":"V\u00e1rnai","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-8976","authenticated-orcid":true,"given":"Julio","family":"Saez-Rodriguez","sequence":"additional","affiliation":[]},{"given":"Ferenc","family":"Jakab","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9320-5704","authenticated-orcid":true,"given":"Bence","family":"Szalai","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"pcbi.1010021.ref001","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An 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