Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro
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 o...
Saved in:
| Published in | International journal of molecular sciences Vol. 22; no. 6; p. 3163 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
MDPI
19.03.2021
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | 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 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), 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. |
|---|---|
| AbstractList | 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 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), 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.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 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), 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. 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( )-hydroxycholesterol, 24( )-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 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), 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. 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 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), 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. 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 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), 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. |
| Author | Ohashi, Hirofumi Watashi, Koichi Suzuki, Tadaki Stappenbeck, Frank Takeda, Makoto Kataoka, Michiyo Sureau, Camille Wakita, Takaji Parhami, Farhad Kobayashi, Chisa Wang, Feng Yamasaki, Masako Saso, Wakana Muramatsu, Masamichi Kuramochi, Kouji Tsuchimoto, Kana |
| AuthorAffiliation | 9 Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan 3 MAX BioPharma, Inc., 2870 Colorado Avenue, Santa Monica, CA 90404, USA; fwang@maxbiopharma.com (F.W.); fstappenbeck@maxbiopharma.com (F.S.) 8 Department of Virology III, National Institute of Infectious Diseases, Tokyo 208-0011, Japan; mtakeda@nih.go.jp 2 Department of Applied Biological Sciences, Tokyo University of Science, Noda 278-8510, Japan; kuramoch@rs.tus.ac.jp 1 Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; hiro4@nih.go.jp (H.O.); kanatcmt@nih.go.jp (K.T.); k-chisa@nih.go.jp (C.K.); wsaso@nih.go.jp (W.S.); mayamasa@nih.go.jp (M.Y.); muramatsu@nih.go.jp (M.M.); wakita@nih.go.jp (T.W.) 7 Laboratoire de Virologie Moléculaire, Institut National de la Transfusion Sanguine, 75739 Paris, France; csureau@ints.fr 10 MIRAI, JST, Kawaguchi Center Building, 4-1-8 Honcho, Kawaguchi City, Saitama 332-0012, Japan 6 Department of Pathology, National Institute o |
| AuthorAffiliation_xml | – name: 7 Laboratoire de Virologie Moléculaire, Institut National de la Transfusion Sanguine, 75739 Paris, France; csureau@ints.fr – name: 10 MIRAI, JST, Kawaguchi Center Building, 4-1-8 Honcho, Kawaguchi City, Saitama 332-0012, Japan – name: 4 The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan – name: 8 Department of Virology III, National Institute of Infectious Diseases, Tokyo 208-0011, Japan; mtakeda@nih.go.jp – name: 6 Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; michiyo@nih.go.jp (M.K.); tksuzuki@nih.go.jp (T.S.) – name: 2 Department of Applied Biological Sciences, Tokyo University of Science, Noda 278-8510, Japan; kuramoch@rs.tus.ac.jp – name: 9 Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan – name: 1 Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; hiro4@nih.go.jp (H.O.); kanatcmt@nih.go.jp (K.T.); k-chisa@nih.go.jp (C.K.); wsaso@nih.go.jp (W.S.); mayamasa@nih.go.jp (M.Y.); muramatsu@nih.go.jp (M.M.); wakita@nih.go.jp (T.W.) – name: 3 MAX BioPharma, Inc., 2870 Colorado Avenue, Santa Monica, CA 90404, USA; fwang@maxbiopharma.com (F.W.); fstappenbeck@maxbiopharma.com (F.S.) – name: 5 AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan |
| Author_xml | – sequence: 1 givenname: Hirofumi surname: Ohashi fullname: Ohashi, Hirofumi – sequence: 2 givenname: Feng surname: Wang fullname: Wang, Feng – sequence: 3 givenname: Frank surname: Stappenbeck fullname: Stappenbeck, Frank – sequence: 4 givenname: Kana surname: Tsuchimoto fullname: Tsuchimoto, Kana – sequence: 5 givenname: Chisa surname: Kobayashi fullname: Kobayashi, Chisa – sequence: 6 givenname: Wakana surname: Saso fullname: Saso, Wakana – sequence: 7 givenname: Michiyo surname: Kataoka fullname: Kataoka, Michiyo – sequence: 8 givenname: Masako surname: Yamasaki fullname: Yamasaki, Masako – sequence: 9 givenname: Kouji orcidid: 0000-0003-0571-9703 surname: Kuramochi fullname: Kuramochi, Kouji – sequence: 10 givenname: Masamichi surname: Muramatsu fullname: Muramatsu, Masamichi – sequence: 11 givenname: Tadaki orcidid: 0000-0002-3820-9542 surname: Suzuki fullname: Suzuki, Tadaki – sequence: 12 givenname: Camille orcidid: 0000-0002-0517-4646 surname: Sureau fullname: Sureau, Camille – sequence: 13 givenname: Makoto orcidid: 0000-0002-8194-7727 surname: Takeda fullname: Takeda, Makoto – sequence: 14 givenname: Takaji surname: Wakita fullname: Wakita, Takaji – sequence: 15 givenname: Farhad surname: Parhami fullname: Parhami, Farhad – sequence: 16 givenname: Koichi surname: Watashi fullname: Watashi, Koichi |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33808940$$D View this record in MEDLINE/PubMed |
| BookMark | eNptUU1v1DAQtVAR_YAbZ-RjKxEY2xvHviCtFgorVaq0C71adjIBV0m82E7E8utJaYsWhOYwM5o372nenJKjIQxIyEsGb4TQ8Nbf9olzkIJJ8YScsAXnBYCsjg7qY3Ka0i0AF7zUz8ixEAqUXsAJ-blucMi-9bXNPgw0tHQ598UWJ4xIl_WYkW4w7Xy0OcQ93e6HJoYeiw12NmNDVyGGwU4-jolyer5dbrbFKtwU_IJe_9injDF09D1GP80KEya6HuiNzzE8J09b2yV88ZDPyJfLD59Xn4qr64_r1fKqqBcl5EKyVlt0EhyTJZeSO-WsBNBO6LYCbVldKscWtVTcusaWqnKNVsyVMEeF4oy8u-fdja7Hpp7vjbYzu-h7G_cmWG_-ngz-m_kaJqMARKXlTHD-QBDD9xFTNr1PNXadHTCMyfASVFkxpdkMfXWo9Ufk0fAZwO8BdQwpRWxN7fNv62dp3xkG5u6r5vCr89Lrf5Yeef8L_wXVlaS7 |
| CitedBy_id | crossref_primary_10_1016_j_jlr_2021_100165 crossref_primary_10_1371_journal_ppat_1011323 crossref_primary_10_1002_eji_202350501 crossref_primary_10_1089_vim_2024_0011 crossref_primary_10_1080_07391102_2023_2205942 crossref_primary_10_1128_spectrum_00566_23 crossref_primary_10_1080_08830185_2024_2314577 crossref_primary_10_1016_j_jsbmb_2021_105996 crossref_primary_10_3389_fimmu_2022_791267 crossref_primary_10_1016_j_jsbmb_2021_105939 crossref_primary_10_1248_bpb_b23_00797 crossref_primary_10_1016_j_bbrc_2023_07_014 crossref_primary_10_1080_07391102_2022_2072392 crossref_primary_10_3389_fimmu_2023_1268854 crossref_primary_10_1016_j_ajcnut_2024_01_017 |
| Cites_doi | 10.1038/s41579-020-0406-z 10.1016/j.bbrc.2004.05.107 10.5501/wjv.v2.i2.32 10.1038/s41467-020-20542-0 10.1038/s41422-020-0282-0 10.1016/j.spinee.2014.11.014 10.1074/jbc.RA118.005033 10.1111/cmi.12372 10.1016/j.redox.2017.03.016 10.1016/j.bbrc.2020.10.094 10.1016/j.immuni.2017.02.012 10.1073/pnas.2002589117 10.3390/cells8050509 10.1016/j.redox.2020.101682 10.1038/s41421-020-0156-0 10.1042/BST20180135 10.1021/acs.jcim.0c00861 10.1002/jbmr.2213 10.1016/j.bbrc.2006.03.059 10.1038/srep07487 10.1126/science.abd3629 10.1002/cbf.3182 10.1016/j.freeradbiomed.2006.12.013 10.1007/s00586-017-5149-9 10.1099/jgv.0.001453 10.1128/JVI.01855-15 10.1371/journal.pone.0215822 10.3390/v11020097 10.3390/cells8101297 10.1016/j.bbrc.2013.12.052 10.1016/j.redox.2018.09.003 10.1016/j.redox.2017.07.014 10.1016/j.jhep.2020.11.032 10.2807/1560-7917.ES.2020.25.3.2000045 |
| ContentType | Journal Article |
| Copyright | 2021 by the authors. 2021 |
| Copyright_xml | – notice: 2021 by the authors. 2021 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.3390/ijms22063163 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE CrossRef |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1422-0067 |
| ExternalDocumentID | PMC8003796 33808940 10_3390_ijms22063163 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: Japan Agency for Medical Research and Development grantid: JP20fk0108274j0201 – fundername: Japan Society for the Promotion of Science grantid: JP20H03499 – fundername: Japan Agency for Medical Research and Development grantid: JP19fk0108111 – fundername: Japan Agency for Medical Research and Development grantid: JP19fk0108156j0101 – fundername: Japan Society for the Promotion of Science grantid: JP20K16267 – fundername: Japan Agency for Medical Research and Development grantid: JP20fk0108104 – fundername: Japan Agency for Medical Research and Development grantid: JP20fk0108179j0101 |
| GroupedDBID | --- 29J 2WC 53G 5GY 5VS 7X7 88E 8FE 8FG 8FH 8FI 8FJ 8G5 A8Z AADQD AAFWJ AAHBH AAYXX ABDBF ABUWG ACGFO ACIHN ACIWK ACPRK ACUHS ADBBV AEAQA AENEX AFKRA AFZYC ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BAWUL BCNDV BENPR BPHCQ BVXVI CCPQU CITATION CS3 D1I DIK DU5 DWQXO E3Z EBD EBS EJD ESX F5P FRP FYUFA GNUQQ GUQSH GX1 HH5 HMCUK HYE IAO IHR ITC KQ8 LK8 M1P M2O M48 MODMG O5R O5S OK1 OVT P2P PHGZM PHGZT PIMPY PQQKQ PROAC PSQYO RNS RPM TR2 TUS UKHRP ~8M CGR CUY CVF ECM EIF NPM 7X8 PPXIY 5PM PJZUB |
| ID | FETCH-LOGICAL-c450t-61f9aeb60b1652662b8ba6009b39f709a1c58b14c682abda587bd981b505057e3 |
| IEDL.DBID | M48 |
| ISSN | 1422-0067 |
| IngestDate | Thu Aug 21 14:39:36 EDT 2025 Fri Jul 11 04:59:05 EDT 2025 Thu Apr 03 07:03:13 EDT 2025 Tue Jul 01 03:07:18 EDT 2025 Thu Apr 24 22:52:31 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6 |
| Keywords | COVID-19 replication SARS-CoV-2 double membrane vesicle oxysterols antiviral pharmacokinetics coronavirus |
| Language | English |
| License | https://creativecommons.org/licenses/by/4.0 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c450t-61f9aeb60b1652662b8ba6009b39f709a1c58b14c682abda587bd981b505057e3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0002-0517-4646 0000-0002-8194-7727 0000-0003-0571-9703 0000-0002-3820-9542 |
| OpenAccessLink | http://journals.scholarsportal.info/openUrl.xqy?doi=10.3390/ijms22063163 |
| PMID | 33808940 |
| PQID | 2508571891 |
| PQPubID | 23479 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_8003796 proquest_miscellaneous_2508571891 pubmed_primary_33808940 crossref_citationtrail_10_3390_ijms22063163 crossref_primary_10_3390_ijms22063163 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 20210319 |
| PublicationDateYYYYMMDD | 2021-03-19 |
| PublicationDate_xml | – month: 3 year: 2021 text: 20210319 day: 19 |
| PublicationDecade | 2020 |
| PublicationPlace | Switzerland |
| PublicationPlace_xml | – name: Switzerland |
| PublicationTitle | International journal of molecular sciences |
| PublicationTitleAlternate | Int J Mol Sci |
| PublicationYear | 2021 |
| Publisher | MDPI |
| Publisher_xml | – name: MDPI |
| References | Iwamoto (ref_6) 2014; 443 (ref_17) 2020; 18 Paul (ref_26) 2013; 2 Luchetti (ref_5) 2017; 13 Cagno (ref_7) 2017; 12 Li (ref_11) 2017; 46 Wolff (ref_18) 2020; 369 Matsuyama (ref_20) 2020; 117 Civra (ref_8) 2014; 4 Ogando (ref_28) 2020; 101 Liu (ref_24) 2020; 6 Kokic (ref_25) 2021; 12 ref_16 ref_15 Goto (ref_30) 2006; 343 Blanchard (ref_19) 2015; 17 Mizutani (ref_32) 2004; 319 Arca (ref_22) 2007; 42 Buser (ref_14) 2017; 26 Ohashi (ref_33) 2018; 293 Scott (ref_13) 2015; 15 Edwards (ref_3) 2020; 60 ref_29 Kaneko (ref_34) 2015; 89 Akpovwa (ref_23) 2016; 34 Wang (ref_2) 2020; 30 ref_9 Montgomery (ref_12) 2014; 29 Marcello (ref_21) 2020; 36 Griffiths (ref_4) 2019; 47 Civra (ref_10) 2018; 19 Corman (ref_31) 2020; 25 Zhang (ref_27) 2021; 74 Watashi (ref_1) 2020; 538 |
| References_xml | – volume: 18 start-page: 411 year: 2020 ident: ref_17 article-title: Coronavirus replication factories publication-title: Nat. Rev. Microbiol. Genet. doi: 10.1038/s41579-020-0406-z – volume: 319 start-page: 1228 year: 2004 ident: ref_32 article-title: Phosphorylation of p38 MAPK and its downstream targets in SARS coronavirus-infected cells publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2004.05.107 – volume: 2 start-page: 32 year: 2013 ident: ref_26 article-title: Architecture and biogenesis of plus-strand RNA virus replication factories publication-title: World J. Virol. doi: 10.5501/wjv.v2.i2.32 – volume: 12 start-page: 279 year: 2021 ident: ref_25 article-title: Mechanism of SARS-CoV-2 polymerase stalling by remdesivir publication-title: Nat. Commun. doi: 10.1038/s41467-020-20542-0 – volume: 30 start-page: 269 year: 2020 ident: ref_2 article-title: Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro publication-title: Cell Res. doi: 10.1038/s41422-020-0282-0 – volume: 15 start-page: 733 year: 2015 ident: ref_13 article-title: Comparison of a novel oxysterol molecule and rhBMP2 fusion rates in a rabbit posterolateral lumbar spine model publication-title: Spine J. doi: 10.1016/j.spinee.2014.11.014 – volume: 293 start-page: 19559 year: 2018 ident: ref_33 article-title: The aryl hydrocarbon receptor–cytochrome P450 1A1 pathway controls lipid accumulation and enhances the permissiveness for hepatitis C virus assembly publication-title: J. Biol. Chem. doi: 10.1074/jbc.RA118.005033 – volume: 17 start-page: 45 year: 2015 ident: ref_19 article-title: Virus-induced double-membrane vesicles publication-title: Cell. Microbiol. doi: 10.1111/cmi.12372 – volume: 12 start-page: 522 year: 2017 ident: ref_7 article-title: Inhibition of herpes simplex-1 virus replication by 25-hydroxycholesterol and 27-hydroxycholesterol publication-title: Redox Biol. doi: 10.1016/j.redox.2017.03.016 – volume: 538 start-page: 137 year: 2020 ident: ref_1 article-title: Identifying and repurposing antiviral drugs against severe acute respiratory syndrome coronavirus 2 with in silico and in vitro approaches publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2020.10.094 – volume: 46 start-page: 446 year: 2017 ident: ref_11 article-title: 25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model publication-title: Immunity doi: 10.1016/j.immuni.2017.02.012 – volume: 117 start-page: 7001 year: 2020 ident: ref_20 article-title: Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.2002589117 – ident: ref_15 doi: 10.3390/cells8050509 – volume: 36 start-page: 101682 year: 2020 ident: ref_21 article-title: The cholesterol metabolite 27-hydroxycholesterol inhibits SARS-CoV-2 and is markedly decreased in COVID-19 patients publication-title: Redox. Biol. doi: 10.1016/j.redox.2020.101682 – volume: 6 start-page: 16 year: 2020 ident: ref_24 article-title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro publication-title: Cell Discov. doi: 10.1038/s41421-020-0156-0 – volume: 47 start-page: 517 year: 2019 ident: ref_4 article-title: Oxysterol research: A brief review publication-title: Biochem. Soc. Trans. doi: 10.1042/BST20180135 – volume: 60 start-page: 5727 year: 2020 ident: ref_3 article-title: What Are the Odds of Finding a COVID-19 Drug from a Lab Repurposing Screen? publication-title: J. Chem. Inf. Model. doi: 10.1021/acs.jcim.0c00861 – volume: 29 start-page: 1872 year: 2014 ident: ref_12 article-title: A Novel Osteogenic Oxysterol Compound for Therapeutic Development to Promote Bone Growth: Activation of Hedgehog Signaling and Osteogenesis Through Smoothened Binding publication-title: J. Bone Miner. Res. doi: 10.1002/jbmr.2213 – volume: 343 start-page: 879 year: 2006 ident: ref_30 article-title: Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811 publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2006.03.059 – volume: 4 start-page: 7487 year: 2014 ident: ref_8 article-title: Inhibition of pathogenic non-enveloped viruses by 25-hydroxycholesterol and 27-hydroxycholesterol publication-title: Sci. Rep. doi: 10.1038/srep07487 – volume: 369 start-page: 1395 year: 2020 ident: ref_18 article-title: A molecular pore spans the double membrane of the coronavirus replication organelle publication-title: Science doi: 10.1126/science.abd3629 – volume: 34 start-page: 191 year: 2016 ident: ref_23 article-title: Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity publication-title: Cell Biochem. Funct. doi: 10.1002/cbf.3182 – volume: 42 start-page: 698 year: 2007 ident: ref_22 article-title: Increased plasma levels of oxysterols, in vivo markers of oxidative stress, in patients with familial combined hyperlipidemia: Reduction during atorvastatin and fenofibrate therapy publication-title: Free. Radic. Biol. Med. doi: 10.1016/j.freeradbiomed.2006.12.013 – volume: 26 start-page: 2763 year: 2017 ident: ref_14 article-title: Effect of Oxy133, an osteogenic oxysterol, on new bone formation in rat two-level posterolateral fusion model publication-title: Eur. Spine J. doi: 10.1007/s00586-017-5149-9 – volume: 101 start-page: 925 year: 2020 ident: ref_28 article-title: SARS-coronavirus-2 replication in Vero E6 cells: Replication kinetics, rapid adaptation and cytopathology publication-title: J. Gen. Virol. doi: 10.1099/jgv.0.001453 – volume: 89 start-page: 11945 year: 2015 ident: ref_34 article-title: A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide publication-title: J. Virol. doi: 10.1128/JVI.01855-15 – ident: ref_29 doi: 10.1371/journal.pone.0215822 – ident: ref_9 doi: 10.3390/v11020097 – ident: ref_16 doi: 10.3390/cells8101297 – volume: 443 start-page: 808 year: 2014 ident: ref_6 article-title: Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2013.12.052 – volume: 19 start-page: 318 year: 2018 ident: ref_10 article-title: 25-Hydroxycholesterol and 27-hydroxycholesterol inhibit human rotavirus infection by sequestering viral particles into late endosomes publication-title: Redox Biol. doi: 10.1016/j.redox.2018.09.003 – volume: 13 start-page: 581 year: 2017 ident: ref_5 article-title: Endothelial cells, endoplasmic reticulum stress and oxysterols publication-title: Redox Biol. doi: 10.1016/j.redox.2017.07.014 – volume: 74 start-page: 686 year: 2021 ident: ref_27 article-title: New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies publication-title: J. Hepatol. doi: 10.1016/j.jhep.2020.11.032 – volume: 25 start-page: 23 year: 2020 ident: ref_31 article-title: Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR publication-title: Eurosurveillance doi: 10.2807/1560-7917.ES.2020.25.3.2000045 |
| SSID | ssj0023259 |
| Score | 2.4195173 |
| Snippet | The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat... |
| SourceID | pubmedcentral proquest pubmed crossref |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | 3163 |
| SubjectTerms | Administration, Oral Animals Antiviral Agents - administration & dosage Antiviral Agents - chemistry Antiviral Agents - pharmacokinetics Antiviral Agents - pharmacology Cell Survival - drug effects Chlorocebus aethiops COVID-19 - drug therapy Mice Nucleocapsid Proteins - drug effects Oxysterols - administration & dosage Oxysterols - chemistry Oxysterols - pharmacokinetics Oxysterols - pharmacology SARS-CoV-2 - drug effects SARS-CoV-2 - genetics Vero Cells Viral Replication Compartments - drug effects Virus Replication - drug effects |
| Title | Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/33808940 https://www.proquest.com/docview/2508571891 https://pubmed.ncbi.nlm.nih.gov/PMC8003796 |
| Volume | 22 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1db9MwFL3ah0B7mfimAyojgQRCHo0bfz1MqJSVgbSBWjr1LbITRxSVBJJ02vj1u27S0jF44SVSFNsPvrbuOfH1OQDPrJIy1amgLBCaIt9w1FiLnEch19AIUWTq7zsfn4ijcfhxwicbsHQbbSaw_Cu1835S42K2f_7z4g1u-APPOJGyv55--14yhrkWscUmbGNOkt7L4DhcnScgbOC6Lnu_1mMHbiJN6yjt_3-s56ZrgPPPusm1RDS4BbsNgiS9OuS3YcNld-BG7Sl5cRd-1Vdv0-ZfHMlT0sN3OnK4aB3pxfPKkeHvA3YyajQL6KIuziWk70UNzNm0mJeEkRej3nBE-_kpZS_Jp3Mv_FzkM_IOV-7ZQjS8JB8ycjqtivwejAeHX_pHtDFYoHHIOxXSxlQbZ0XHBoJjpmZWWYMISNuuTmVHmyDmygZhLBQzNjFcSZtoBLrc-99J170PW1meuYdAukqkKXcBDpyEYWKVlkEiEoHTHTNtkha8Wk5tFDfq494EYxYhC_ExidZj0oLnq9Y_atWNf7R7uoxShNvCn3WYzOXzMkJkpzjmXR204EEdtdVIy3C3QF6J56qBl9y--iWbfl1Ibyuv16PF3n_3fAQ7zFfF-IpA_Ri2qmLuniCsqWwbNuVE4lMN3rdh--3hyedh2yca3l6s5UuGmv4A |
| linkProvider | Scholars Portal |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+Anti-Severe+Acute+Respiratory+Syndrome-Related+Coronavirus+2+%28SARS-CoV-2%29+Oxysterol+Derivatives+In+Vitro&rft.jtitle=International+journal+of+molecular+sciences&rft.au=Ohashi%2C+Hirofumi&rft.au=Wang%2C+Feng&rft.au=Stappenbeck%2C+Frank&rft.au=Tsuchimoto%2C+Kana&rft.date=2021-03-19&rft.pub=MDPI&rft.eissn=1422-0067&rft.volume=22&rft.issue=6&rft_id=info:doi/10.3390%2Fijms22063163&rft_id=info%3Apmid%2F33808940&rft.externalDocID=PMC8003796 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1422-0067&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1422-0067&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1422-0067&client=summon |