{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:41:55Z","timestamp":1785307315719,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011323","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["200838\/Z\/16\/Z"],"award-info":[{"award-number":["200838\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R022011\/1"],"award-info":[{"award-number":["MR\/R022011\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","award":["2018-I2M-2-002"],"award-info":[{"award-number":["2018-I2M-2-002"]}],"id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oxford Medical Science Division Internal Research Fund","award":["0011162"],"award-info":[{"award-number":["0011162"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["214191\/Z\/18\/Z"],"award-info":[{"award-number":["214191\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["26603"],"award-info":[{"award-number":["26603"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023449","name":"UK Coronavirus Immunology Consortium","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017158","name":"Royal Free Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017158","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C2195\/A27431"],"award-info":[{"award-number":["C2195\/A27431"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T001313\/1"],"award-info":[{"award-number":["MR\/T001313\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/V027506\/1"],"award-info":[{"award-number":["MR\/V027506\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W005611\/1"],"award-info":[{"award-number":["MR\/W005611\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["5F40120C00085"],"award-info":[{"award-number":["5F40120C00085"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","award":["044-0001"],"award-info":[{"award-number":["044-0001"]}],"id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["BB\/R019843\/1, BBS\/E\/I\/00007034 and BB\/T008784\/1"],"award-info":[{"award-number":["BB\/R019843\/1, BBS\/E\/I\/00007034 and BB\/T008784\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21fk0108589"],"award-info":[{"award-number":["JP21fk0108589"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104553\/z\/14\/z, 211050\/Z\/18\/z"],"award-info":[{"award-number":["104553\/z\/14\/z, 211050\/Z\/18\/z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and\/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects.<\/jats:p>\n<jats:p><jats:bold>Trial registration<\/jats:bold>: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04318314\" xlink:type=\"simple\">NCT04318314<\/jats:ext-link>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011323","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T17:40:26Z","timestamp":1683135626000},"page":"e1011323","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity"],"prefix":"10.1371","volume":"19","author":[{"given":"Peter A. C.","family":"Wing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie M.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Erdmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Swadling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"COVIDsortium Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia","family":"Thakur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaho","family":"Shionoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie B.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy SC","family":"Hinks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Watashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalan","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-1462","authenticated-orcid":true,"given":"Mala K.","family":"Maini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-5886","authenticated-orcid":true,"given":"Jane A.","family":"McKeating","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"ppat.1011323.ref001","unstructured":"WHO. WHO Coronavirus (COVID-19) Dashboard 13.10.2022. [cited 13 Oct 2022]. Available: https:\/\/covid19.who.int"},{"key":"ppat.1011323.ref002","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1377\/hlthaff.2021.00619","article-title":"Vaccinations Against COVID-19 May Have Averted Up To 140,000 Deaths In The United States.","volume":"40","author":"S Gupta","year":"2021","journal-title":"Health Affairs."},{"key":"ppat.1011323.ref003","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(21)01358-1","article-title":"SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness","volume":"397","author":"A Sheikh","year":"2021","journal-title":"The Lancet"},{"key":"ppat.1011323.ref004","unstructured":"NIH. COVID-19 Treatment Guidelines 13.10.2022. 13 Oct 2022. Available: https:\/\/www.covid19treatmentguidelines.nih.gov\/"},{"key":"ppat.1011323.ref005","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.cell.2020.09.038","article-title":"Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity","volume":"183","author":"CR Moderbacher","year":"2020","journal-title":"Cell"},{"key":"ppat.1011323.ref006","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41590-021-01122-w","article-title":"The T cell immune response against SARS-CoV-2","volume":"23","author":"P. Moss","year":"2022","journal-title":"Nat Immunol"},{"key":"ppat.1011323.ref007","article-title":"Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2","author":"L Swadling","year":"2021","journal-title":"Nature"},{"key":"ppat.1011323.ref008","doi-asserted-by":"crossref","first-page":"108728","DOI":"10.1016\/j.celrep.2021.108728","article-title":"Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients","volume":"34","author":"AT Tan","year":"2021","journal-title":"Cell Reports"},{"key":"ppat.1011323.ref009","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41590-021-01084-z","article-title":"An immunodominant NP105\u2013113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease","volume":"23","author":"Y Peng","year":"2022","journal-title":"Nature Immunology"},{"key":"ppat.1011323.ref010","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41577-020-0402-6","article-title":"T cell responses in patients with COVID-19","volume":"20","author":"Z Chen","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"ppat.1011323.ref011","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/s41591-020-1038-6","article-title":"A dynamic COVID-19 immune signature includes associations with poor prognosis","volume":"26","author":"AG Laing","year":"2020","journal-title":"Nature Medicine"},{"key":"ppat.1011323.ref012","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1172\/JCI138554","article-title":"Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent","volume":"130","author":"A Mazzoni","year":"2020","journal-title":"J Clin Invest"},{"key":"ppat.1011323.ref013","doi-asserted-by":"crossref","first-page":"e1003820","DOI":"10.1371\/journal.pmed.1003820","article-title":"HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: A registry-based cohort study.","volume":"18","author":"R Bergqvist","year":"2021","journal-title":"PLOS Medicine"},{"key":"ppat.1011323.ref014","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1038\/s41467-021-21553-1","article-title":"Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19.","volume":"12","author":"A Gupta","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1011323.ref015","first-page":"1","article-title":"Cholesterol-modifying drugs in COVID-19","author":"NM Schmidt","year":"2020","journal-title":"Oxford Open Immunology"},{"key":"ppat.1011323.ref016","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nrm2336","article-title":"Cellular cholesterol trafficking and compartmentalization","volume":"9","author":"E. Ikonen","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ppat.1011323.ref017","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/ni.2570","article-title":"Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity","volume":"14","author":"Y Kidani","year":"2013","journal-title":"Nat Immunol"},{"key":"ppat.1011323.ref018","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/ni.2681","article-title":"Sterols and oxysterols in immune cell function","volume":"14","author":"NJ Spann","year":"2013","journal-title":"Nat Immunol"},{"key":"ppat.1011323.ref019","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.750544","article-title":"Endosomal Cholesterol in Viral Infections\u2013A Common Denominator?","volume":"12","author":"M Glitscher","year":"2021","journal-title":"Frontiers in Physiology."},{"key":"ppat.1011323.ref020","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cell.2020.10.030","article-title":"Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells","volume":"184","author":"Z Daniloski","year":"2021","journal-title":"Cell"},{"key":"ppat.1011323.ref021","doi-asserted-by":"crossref","first-page":"796855","DOI":"10.3389\/fimmu.2021.796855","article-title":"Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry.","volume":"12","author":"SN Palacios-R\u00e1palo","year":"2021","journal-title":"Front Immunol."},{"key":"ppat.1011323.ref022","doi-asserted-by":"crossref","first-page":"e65962","DOI":"10.7554\/eLife.65962","article-title":"SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation.","volume":"10","author":"DW Sanders","year":"2021","journal-title":"eLife"},{"key":"ppat.1011323.ref023","doi-asserted-by":"crossref","first-page":"e0170123","DOI":"10.1371\/journal.pone.0170123","article-title":"The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain.","author":"H Guo","year":"2017","journal-title":"PLoS One."},{"key":"ppat.1011323.ref024","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1007\/s00705-018-3967-7","article-title":"Cholesterol is important for the entry process of porcine deltacoronavirus","author":"JH Jeon","year":"2018","journal-title":"Arch Virol"},{"key":"ppat.1011323.ref025","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.bbrc.2008.02.023","article-title":"Lipid rafts are involved in SARS-CoV entry into Vero E6 cells","author":"Y Lu","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"ppat.1011323.ref026","article-title":"The role of high cholesterol in age-related COVID19 lethality.","author":"H Wang","year":"2021","journal-title":"bioRxiv."},{"key":"ppat.1011323.ref027","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s42003-022-03841-8","article-title":"Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture","author":"Z Yuan","year":"2022","journal-title":"Commun Biol"},{"key":"ppat.1011323.ref028","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s42255-020-00324-0","article-title":"HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.","volume":"2","author":"C Wei","year":"2020","journal-title":"Nature Metabolism."},{"key":"ppat.1011323.ref029","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cell.2020.12.004","article-title":"Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses","volume":"184","author":"R Wang","year":"2021","journal-title":"Cell"},{"key":"ppat.1011323.ref030","article-title":"Viral and Host Transcriptomes in SARS-CoV-2-","author":"X Wang","year":"2021","journal-title":"Infected Human Lung Cells"},{"key":"ppat.1011323.ref031","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.chom.2020.12.009","article-title":"Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.","volume":"29","author":"H-H Hoffmann","year":"2021","journal-title":"Cell Host & Microbe."},{"key":"ppat.1011323.ref032","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.cell.2020.12.006","article-title":"Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks","volume":"184","author":"WM Schneider","year":"2021","journal-title":"Cell"},{"key":"ppat.1011323.ref033","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41588-021-00805-2","article-title":"Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2","volume":"53","author":"J Baggen","year":"2021","journal-title":"Nature Genetics"},{"key":"ppat.1011323.ref034","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cell.2020.10.030","article-title":"Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells","volume":"184","author":"Z Daniloski","year":"2021","journal-title":"Cell"},{"key":"ppat.1011323.ref035","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5501\/wjv.v2.i2.32","article-title":"Architecture and biogenesis of plus-strand RNA virus replication factories","volume":"2","author":"D Paul","year":"2013","journal-title":"World journal of virology"},{"key":"ppat.1011323.ref036","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.3390\/ijms22063163","article-title":"Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro.","volume":"22","author":"H Ohashi","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"ppat.1011323.ref037","doi-asserted-by":"crossref","first-page":"11181","DOI":"10.1128\/JVI.01053-16","article-title":"The Intracellular Cholesterol Transport Inhibitor U18666A Inhibits the Exosome-Dependent Release of Mature Hepatitis C Virus","volume":"90","author":"F Elgner","year":"2016","journal-title":"Journal of Virology"},{"key":"ppat.1011323.ref038","article-title":"Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection.","volume":"4","author":"F Lu","year":"2015","journal-title":"eLife"},{"key":"ppat.1011323.ref039","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.antiviral.2011.11.014","article-title":"U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication","volume":"93","author":"MK Poh","year":"2012","journal-title":"Antiviral Research"},{"key":"ppat.1011323.ref040","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.antiviral.2017.07.022","article-title":"The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection","volume":"145","author":"T Takano","year":"2017","journal-title":"Antiviral Research"},{"key":"ppat.1011323.ref041","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.antiviral.2017.10.016","article-title":"Avasimibe: A novel hepatitis C virus inhibitor that targets the assembly of infectious viral particles","volume":"148","author":"L Hu","year":"2017","journal-title":"Antiviral Res"},{"key":"ppat.1011323.ref042","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1038\/s41467-021-22967-7","article-title":"Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint","volume":"12","author":"NM Schmidt","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1011323.ref043","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nature17412","article-title":"Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism.","volume":"531","author":"W Yang","year":"2016","journal-title":"Nature"},{"key":"ppat.1011323.ref044","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.molcel.2020.04.022","article-title":"A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells","volume":"78","author":"M Hoffmann","year":"2020","journal-title":"Molecular Cell"},{"key":"ppat.1011323.ref045","first-page":"e00127","article-title":"Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus","volume":"94","author":"Y Wan","year":"2020","journal-title":"Journal of Virology"},{"key":"ppat.1011323.ref046","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"CB Jackson","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ppat.1011323.ref047","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/s41564-021-00908-w","article-title":"The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets","volume":"6","author":"TP Peacock","year":"2021","journal-title":"Nature Microbiology"},{"key":"ppat.1011323.ref048","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1146\/annurev-cellbio-101512-122422","article-title":"Virus and Cell Fusion Mechanisms.","volume":"30","author":"B Podbilewicz","year":"2014","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ppat.1011323.ref049","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41586-019-0987-8","article-title":"Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma","volume":"567","author":"Y Jiang","year":"2019","journal-title":"Nature"},{"key":"ppat.1011323.ref050","doi-asserted-by":"crossref","first-page":"e1010343","DOI":"10.1371\/journal.ppat.1010343","article-title":"Diltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung","volume":"18","author":"X Wang","year":"2022","journal-title":"PLOS Pathogens"},{"key":"ppat.1011323.ref051","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41421-020-00222-5","article-title":"Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro","volume":"6","author":"Q Zhang","year":"2020","journal-title":"Cell Discovery"},{"key":"ppat.1011323.ref052","article-title":"Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.","author":"K-YA Huang","year":"2020","journal-title":"bioRxiv."},{"key":"ppat.1011323.ref053","article-title":"Development of SARS-CoV-2 replicons for the ancestral virus and variant of concern Delta for antiviral screening.","author":"M Erdmann","year":"2022","journal-title":"bioRxiv."},{"key":"ppat.1011323.ref054","article-title":"Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences","volume":"11","author":"JY Lee","year":"2022","journal-title":"eLife"},{"key":"ppat.1011323.ref055","doi-asserted-by":"crossref","first-page":"e1010807","DOI":"10.1371\/journal.ppat.1010807","article-title":"Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.","volume":"18","author":"PAC Wing","year":"2022","journal-title":"PLOS Pathogens"},{"key":"ppat.1011323.ref056","doi-asserted-by":"crossref","first-page":"8969","DOI":"10.1021\/jm3012189","article-title":"Inhibition of Acyl-CoA: Cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid \u03b2 (A\u03b2) oligomers-induced neuronal cell death by tricyclic pyrone molecules.","volume":"55","author":"L Pokhrel","year":"2012","journal-title":"Journal of Medicinal Chemistry"},{"key":"ppat.1011323.ref057","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1161\/ATVBAHA.111.223552","article-title":"Pyripyropene A, an acyl-coenzyme A:cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia","volume":"31","author":"T Ohshiro","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ppat.1011323.ref058","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1210\/en.2015-2052","article-title":"ATR-101, a Selective and Potent Inhibitor of Acyl-CoA Acyltransferase 1, Induces Apoptosis in H295R Adrenocortical Cells and in the Adrenal Cortex of Dogs","volume":"157","author":"CR LaPensee","year":"2016","journal-title":"Endocrinology"},{"key":"ppat.1011323.ref059","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/s41591-020-0944-y","article-title":"A single-cell atlas of the peripheral immune response in patients with severe COVID-19","volume":"26","author":"AJ Wilk","year":"2020","journal-title":"Nature Medicine"},{"key":"ppat.1011323.ref060","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1038\/s41467-021-22967-7","article-title":"Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint","volume":"12","author":"NM Schmidt","year":"2021","journal-title":"Nature Communications"},{"key":"ppat.1011323.ref061","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.jhep.2014.07.005","article-title":"Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation","volume":"61","author":"B Bengsch","year":"2014","journal-title":"J Hepatol"},{"key":"ppat.1011323.ref062","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S2468-1253(18)30007-4","article-title":"Defective T-cell immunity in hepatitis B virus infection: why therapeutic vaccination needs a helping hand.","volume":"3","author":"MK Maini","year":"2018","journal-title":"The Lancet Gastroenterology & Hepatology."},{"key":"ppat.1011323.ref063","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41577-020-0348-8","article-title":"Considering how biological sex impacts immune responses and COVID-19 outcomes","volume":"20","author":"EP Scully","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"ppat.1011323.ref064","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area","volume":"323","author":"S Richardson","year":"2020","journal-title":"JAMA"},{"key":"ppat.1011323.ref065","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1527-3466.2003.tb00104.x","article-title":"Pharmacology of the ACAT inhibitor avasimibe (CI-1011).","volume":"21","author":"G Llaver\u00edas","year":"2003","journal-title":"Cardiovasc Drug Rev."},{"key":"ppat.1011323.ref066","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-virology-092818-015756","article-title":"Interferon-Stimulated Genes: What Do They All Do?","volume":"6","author":"JW Schoggins","year":"2019","journal-title":"Annu Rev Virol."},{"key":"ppat.1011323.ref067","doi-asserted-by":"crossref","first-page":"e106057","DOI":"10.15252\/embj.2020106057","article-title":"Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol","volume":"39","author":"S Wang","year":"2020","journal-title":"The EMBO Journal"},{"key":"ppat.1011323.ref068","doi-asserted-by":"crossref","first-page":"32105","DOI":"10.1073\/pnas.2012197117","article-title":"Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion","volume":"117","author":"R Zang","year":"2020","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ppat.1011323.ref069","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/s41422-020-00398-1","article-title":"25-Hydroxycholesterol is a potent SARS-CoV-2 inhibitor","volume":"30","author":"S Zu","year":"2020","journal-title":"Cell Research"},{"key":"ppat.1011323.ref070","doi-asserted-by":"crossref","first-page":"796855","DOI":"10.3389\/fimmu.2021.796855","article-title":"Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry.","volume":"12","author":"SN Palacios-R\u00e1palo","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"ppat.1011323.ref071","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1637\/0005-2086(2007)051[0045:HSIASA]2.0.CO;2","article-title":"Heparan sulfate is a selective attachment factor for the avian coronavirus infectious bronchitis virus Beaudette","volume":"51","author":"IG Madu","year":"2007","journal-title":"Avian diseases"},{"key":"ppat.1011323.ref072","doi-asserted-by":"crossref","first-page":"e23710","DOI":"10.1371\/journal.pone.0023710","article-title":"Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans","volume":"6","author":"J Lang","year":"2011","journal-title":"PLoS ONE"},{"key":"ppat.1011323.ref073","doi-asserted-by":"crossref","first-page":"14451","DOI":"10.1128\/JVI.79.22.14451-14456.2005","article-title":"Murine coronavirus with an extended host range uses heparan sulfate as an entry receptor.","volume":"79","author":"CAM de Haan","year":"2005","journal-title":"Journal of Virology"},{"key":"ppat.1011323.ref074","first-page":"35","article-title":"Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells","author":"PAC Wing","year":"2021","journal-title":"Cell Reports"},{"key":"ppat.1011323.ref075","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.cell.2020.05.042","article-title":"SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract","volume":"182","author":"YJ Hou","year":"2020","journal-title":"Cell"},{"key":"ppat.1011323.ref076","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jsbmb.2014.09.008","article-title":"Acyl-CoA:cholesterol acyltransferases (ACATs\/SOATs): Enzymes with multiple sterols as substrates and as activators.","volume":"151","author":"MA Rogers","year":"2015","journal-title":"The Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ppat.1011323.ref077","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41590-020-0782-6","article-title":"Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19","volume":"21","author":"Y Peng","year":"2020","journal-title":"Nat Immunol"},{"key":"ppat.1011323.ref078","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41586-021-03739-1","article-title":"Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2","volume":"596","author":"DA Collier","year":"2021","journal-title":"Nature"},{"key":"ppat.1011323.ref079","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1113\/jphysiol.1928.sp002523","article-title":"The cholesterol content of normal tissues and the effect of intravenous injections of cholesterol thereon","volume":"66","author":"EN Chamberlain","year":"1928","journal-title":"The Journal of Physiology"},{"key":"ppat.1011323.ref080","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1529\/biophysj.106.099762","article-title":"Effect of Cholesterol on the Biophysical and Physiological Properties of a Clinical Pulmonary Surfactant","volume":"93","author":"E Keating","year":"2007","journal-title":"Biophysical Journal"},{"key":"ppat.1011323.ref081","doi-asserted-by":"crossref","first-page":"2000685","DOI":"10.2807\/1560-7917.ES.2020.25.42.2000685","article-title":"Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020.","volume":"25","author":"CP Thompson","year":"2020","journal-title":"Eurosurveillance."},{"key":"ppat.1011323.ref082","doi-asserted-by":"crossref","first-page":"e3001091","DOI":"10.1371\/journal.pbio.3001091","article-title":"A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research","volume":"19","author":"SJ Rihn","year":"2021","journal-title":"PLOS Biology"},{"key":"ppat.1011323.ref083","article-title":"Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.","author":"JB Augusto","year":"2020","journal-title":"Wellcome Open Research"},{"key":"ppat.1011323.ref084","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abf3698","article-title":"Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection","volume":"5","author":"CJ Reynolds","year":"2020","journal-title":"Science Immunology"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011323","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011323","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T17:39:37Z","timestamp":1684777177000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011323"}},"subtitle":[],"editor":[{"given":"Stephanie","family":"Pfaender","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":84,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011323","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1011323","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,3]]}}}