{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:17:24Z","timestamp":1780586244388,"version":"3.54.1"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Finland and the Sigrid Jus\u00e9lius Foundation"},{"DOI":"10.13039\/501100005416","name":"Norwegian Research Council","doi-asserted-by":"publisher","award":["105572"],"award-info":[{"award-number":["105572"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norwegian Research Council","doi-asserted-by":"publisher","award":["237718"],"award-info":[{"award-number":["237718"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Laboratory Medicine and Pathology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The ongoing coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to better understand virus\u2013host interactions. We developed a network-based method that expands the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)\u2013host protein interaction network and identifies host targets that modulate viral infection. To disrupt the SARS-CoV-2 interactome, we systematically probed for potent compounds that selectively target the identified host proteins with high expression in cells relevant to COVID-19. We experimentally tested seven chemical inhibitors of the identified host proteins for modulation of SARS-CoV-2 infection in human cells that express ACE2 and TMPRSS2. Inhibition of the epigenetic regulators bromodomain-containing protein 4 (BRD4) and histone deacetylase 2 (HDAC2), along with ubiquitin-specific peptidase (USP10), enhanced SARS-CoV-2 infection. Such proviral effect was observed upon treatment with compounds JQ1, vorinostat, romidepsin and spautin-1, when measured by cytopathic effect and validated by viral RNA assays, suggesting that the host proteins HDAC2, BRD4 and USP10 have antiviral functions. We observed marked differences in antiviral effects across cell lines, which may have consequences for identification of selective modulators of viral infection or potential antiviral therapeutics. While network-based approaches enable systematic identification of host targets and selective compounds that may modulate the SARS-CoV-2 interactome, further developments are warranted to increase their accuracy and cell-context specificity.<\/jats:p>","DOI":"10.1093\/bib\/bbac456","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T11:43:58Z","timestamp":1664279038000},"source":"Crossref","is-referenced-by-count":15,"title":["Discovery of host-directed modulators of virus infection by probing the SARS-CoV-2\u2013host protein\u2013protein interaction network"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-9433","authenticated-orcid":false,"given":"Vandana","family":"Ravindran","sequence":"first","affiliation":[{"name":"Oslo Centre for Biostatistics and Epidemiology (OCBE), Faculty of Medicine, University of Oslo , Oslo, Norway"},{"name":"Institute for Cancer Research, Department of Cancer Genetics, Oslo University Hospital , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Wagoner","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine & Pathology, University of Washington , Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paschalis","family":"Athanasiadis","sequence":"additional","affiliation":[{"name":"Oslo Centre for Biostatistics and Epidemiology (OCBE), Faculty of Medicine, University of Oslo , Oslo, Norway"},{"name":"Institute for Cancer Research, Department of Cancer Genetics, Oslo University Hospital , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas B","family":"Den Hartigh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine & Pathology, University of Washington , Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia 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Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"White","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Department of Microbiology, University of Virginia , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Polyak","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine & Pathology, University of Washington , Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero","family":"Aittokallio","sequence":"additional","affiliation":[{"name":"Oslo Centre for Biostatistics and Epidemiology (OCBE), Faculty of Medicine, University of Oslo , Oslo, Norway"},{"name":"Institute for Cancer Research, Department of Cancer Genetics, Oslo University Hospital , Oslo, Norway"},{"name":"Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki , Helsinki, 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