{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:12:31Z","timestamp":1783487551447,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk0108111"],"award-info":[{"award-number":["JP19fk0108111"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk0108156j0101"],"award-info":[{"award-number":["JP19fk0108156j0101"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20fk0108179j0101"],"award-info":[{"award-number":["JP20fk0108179j0101"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20fk0108274j0201"],"award-info":[{"award-number":["JP20fk0108274j0201"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20fk0108104"],"award-info":[{"award-number":["JP20fk0108104"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H03499"],"award-info":[{"award-number":["JP20H03499"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K16267"],"award-info":[{"award-number":["JP20K16267"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 \u03bcM and 99% at 15 \u03bcM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 \u03bcM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.<\/jats:p>","DOI":"10.3390\/ijms22063163","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T22:00:37Z","timestamp":1616364037000},"page":"3163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro"],"prefix":"10.3390","volume":"22","author":[{"given":"Hirofumi","family":"Ohashi","sequence":"first","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan"},{"name":"Department of Applied Biological Sciences, Tokyo University of Science, Noda 278-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"MAX BioPharma, Inc., 2870 Colorado Avenue, Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Stappenbeck","sequence":"additional","affiliation":[{"name":"MAX BioPharma, Inc., 2870 Colorado Avenue, Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Tsuchimoto","sequence":"additional","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisa","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan"},{"name":"Department of Applied Biological Sciences, Tokyo University of Science, Noda 278-8510, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0571-9703","authenticated-orcid":false,"given":"Kouji","family":"Kuramochi","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Sciences, Tokyo University of Science, Noda 278-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-9542","authenticated-orcid":false,"given":"Tadaki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0517-4646","authenticated-orcid":false,"given":"Camille","family":"Sureau","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie Mol\u00e9culaire, Institut National de la Transfusion Sanguine, 75739 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8194-7727","authenticated-orcid":false,"given":"Makoto","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Virology III, National Institute of Infectious Diseases, Tokyo 208-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaji","family":"Wakita","sequence":"additional","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbrc.2020.10.094","article-title":"Identifying and repurposing antiviral drugs against severe acute respiratory syndrome coronavirus 2 with in silico and in vitro approaches","volume":"538","author":"Watashi","year":"2020","journal-title":"Biochem. 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