Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 re...
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| Veröffentlicht in: | Science advances 2022-02, Vol.8 (8), p.eabi6110 |
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| creator | Nguyen, Long Chi Yang, Dongbo Nicolaescu, Vlad Best, Thomas J Gula, Haley Saxena, Divyasha Gabbard, Jon D Chen, Shao-Nong Ohtsuki, Takashi Friesen, John Brent Drayman, Nir Mohamed, Adil Dann, Christopher Silva, Diane Robinson-Mailman, Lydia Valdespino, Andrea Stock, Letícia Suárez, Eva Jones, Krysten A Azizi, Saara-Anne Demarco, Jennifer K Severson, William E Anderson, Charles D Millis, James Michael Dickinson, Bryan C Tay, Savaş Oakes, Scott A Pauli, Guido F Palmer, Kenneth E Meltzer, David O Randall, Glenn Rosner, Marsha Rich |
| description | The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time. |
| doi_str_mv | 10.1126/sciadv.abi6110 |
| format | Article |
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Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.abi6110</identifier><identifier>PMID: 35050692</identifier><language>eng</language><publisher>United States</publisher><subject>A549 Cells ; Animals ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Cannabidiol - chemistry ; Cannabidiol - metabolism ; Cannabidiol - pharmacology ; Chlorocebus aethiops ; COVID-19 - drug therapy ; COVID-19 - virology ; Endoplasmic Reticulum Stress - drug effects ; Endoribonucleases - genetics ; Endoribonucleases - metabolism ; Epithelial Cells - virology ; Female ; Gene Expression Regulation, Viral - drug effects ; Host-Pathogen Interactions - drug effects ; Host-Pathogen Interactions - physiology ; Humans ; Immunity, Innate - drug effects ; Interferons - metabolism ; Mice ; Protein Serine-Threonine Kinases - genetics ; Protein Serine-Threonine Kinases - metabolism ; SARS-CoV-2 - drug effects ; SARS-CoV-2 - physiology ; Vero Cells ; Virus Internalization - drug effects ; Virus Replication - drug effects</subject><ispartof>Science advances, 2022-02, Vol.8 (8), p.eabi6110</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c335t-5740ba4311311fc30201b2287784baf30757a325ff94cf35a7e13b54f674588f3</citedby><cites>FETCH-LOGICAL-c335t-5740ba4311311fc30201b2287784baf30757a325ff94cf35a7e13b54f674588f3</cites><orcidid>0000-0002-8343-5477 ; 0000-0002-0739-9224 ; 0000-0002-2811-1111 ; 0000-0003-2099-2249 ; 0000-0002-4637-2331 ; 0000-0002-1912-6020 ; 0000-0003-0654-6250 ; 0000-0002-6347-0232 ; 0000-0003-0711-5516 ; 0000-0002-5361-5776 ; 0000-0002-8475-7435 ; 0000-0003-4460-9558 ; 0000-0001-7417-3615 ; 0000-0002-9616-1911 ; 0000-0002-6302-1373 ; 0000-0003-1022-4326 ; 0000-0003-0748-0863 ; 0000-0003-2790-7393 ; 0000-0002-9226-9917 ; 0000-0001-6586-8335 ; 0000-0003-4807-6250</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35050692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nguyen, Long Chi</creatorcontrib><creatorcontrib>Yang, Dongbo</creatorcontrib><creatorcontrib>Nicolaescu, Vlad</creatorcontrib><creatorcontrib>Best, Thomas J</creatorcontrib><creatorcontrib>Gula, Haley</creatorcontrib><creatorcontrib>Saxena, Divyasha</creatorcontrib><creatorcontrib>Gabbard, Jon D</creatorcontrib><creatorcontrib>Chen, Shao-Nong</creatorcontrib><creatorcontrib>Ohtsuki, Takashi</creatorcontrib><creatorcontrib>Friesen, John Brent</creatorcontrib><creatorcontrib>Drayman, Nir</creatorcontrib><creatorcontrib>Mohamed, Adil</creatorcontrib><creatorcontrib>Dann, Christopher</creatorcontrib><creatorcontrib>Silva, Diane</creatorcontrib><creatorcontrib>Robinson-Mailman, Lydia</creatorcontrib><creatorcontrib>Valdespino, Andrea</creatorcontrib><creatorcontrib>Stock, Letícia</creatorcontrib><creatorcontrib>Suárez, Eva</creatorcontrib><creatorcontrib>Jones, Krysten A</creatorcontrib><creatorcontrib>Azizi, Saara-Anne</creatorcontrib><creatorcontrib>Demarco, Jennifer K</creatorcontrib><creatorcontrib>Severson, William E</creatorcontrib><creatorcontrib>Anderson, Charles D</creatorcontrib><creatorcontrib>Millis, James Michael</creatorcontrib><creatorcontrib>Dickinson, Bryan C</creatorcontrib><creatorcontrib>Tay, Savaş</creatorcontrib><creatorcontrib>Oakes, Scott A</creatorcontrib><creatorcontrib>Pauli, Guido F</creatorcontrib><creatorcontrib>Palmer, Kenneth E</creatorcontrib><creatorcontrib>Meltzer, David O</creatorcontrib><creatorcontrib>Randall, Glenn</creatorcontrib><creatorcontrib>Rosner, Marsha Rich</creatorcontrib><creatorcontrib>National COVID Cohort Collaborative Consortium</creatorcontrib><creatorcontrib>The National COVID Cohort Collaborative Consortium</creatorcontrib><title>Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. 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drug effects</subject><subject>Interferons - metabolism</subject><subject>Mice</subject><subject>Protein Serine-Threonine Kinases - genetics</subject><subject>Protein Serine-Threonine Kinases - metabolism</subject><subject>SARS-CoV-2 - drug effects</subject><subject>SARS-CoV-2 - physiology</subject><subject>Vero Cells</subject><subject>Virus Internalization - drug effects</subject><subject>Virus Replication - drug effects</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkF1LwzAYhYMobszdein5A635bLrLUeYHDIRNvS1pm9jImpQkFfz3RjdFeOG8HM45Fw8A1xjlGJPiNrRGdh-5bEyBMToDc0IFzwhn5fm_fwaWIbwjhDArCo5Xl2BGOeKoWJE5cJW0Ng10xh2gsb1pTAxwv97ts8q9ZgR6NR5MK6NxFsbeu-mtT7luan8cp5OpYO9ChJsdDNGrEKC0XcpYGRU0wzBZlVbC6GxQ4QpcaHkIannSBXi52zxXD9n26f6xWm-zllIeMy4YaiSjGKfTLUUE4YaQUoiSNVJTJLiQlHCtV6zVlEuhMG0404VgvCw1XYD8uNt6F4JXuh69GaT_rDGqv-HVR3j1CV4q3BwL49QMqvuL_6KiXxBZbIY</recordid><startdate>20220225</startdate><enddate>20220225</enddate><creator>Nguyen, Long Chi</creator><creator>Yang, Dongbo</creator><creator>Nicolaescu, Vlad</creator><creator>Best, Thomas J</creator><creator>Gula, Haley</creator><creator>Saxena, Divyasha</creator><creator>Gabbard, Jon D</creator><creator>Chen, Shao-Nong</creator><creator>Ohtsuki, Takashi</creator><creator>Friesen, John Brent</creator><creator>Drayman, Nir</creator><creator>Mohamed, Adil</creator><creator>Dann, Christopher</creator><creator>Silva, Diane</creator><creator>Robinson-Mailman, Lydia</creator><creator>Valdespino, Andrea</creator><creator>Stock, Letícia</creator><creator>Suárez, Eva</creator><creator>Jones, Krysten A</creator><creator>Azizi, Saara-Anne</creator><creator>Demarco, Jennifer K</creator><creator>Severson, William E</creator><creator>Anderson, Charles D</creator><creator>Millis, James Michael</creator><creator>Dickinson, Bryan C</creator><creator>Tay, Savaş</creator><creator>Oakes, Scott A</creator><creator>Pauli, Guido F</creator><creator>Palmer, Kenneth E</creator><creator>Meltzer, David O</creator><creator>Randall, Glenn</creator><creator>Rosner, Marsha Rich</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-8343-5477</orcidid><orcidid>https://orcid.org/0000-0002-0739-9224</orcidid><orcidid>https://orcid.org/0000-0002-2811-1111</orcidid><orcidid>https://orcid.org/0000-0003-2099-2249</orcidid><orcidid>https://orcid.org/0000-0002-4637-2331</orcidid><orcidid>https://orcid.org/0000-0002-1912-6020</orcidid><orcidid>https://orcid.org/0000-0003-0654-6250</orcidid><orcidid>https://orcid.org/0000-0002-6347-0232</orcidid><orcidid>https://orcid.org/0000-0003-0711-5516</orcidid><orcidid>https://orcid.org/0000-0002-5361-5776</orcidid><orcidid>https://orcid.org/0000-0002-8475-7435</orcidid><orcidid>https://orcid.org/0000-0003-4460-9558</orcidid><orcidid>https://orcid.org/0000-0001-7417-3615</orcidid><orcidid>https://orcid.org/0000-0002-9616-1911</orcidid><orcidid>https://orcid.org/0000-0002-6302-1373</orcidid><orcidid>https://orcid.org/0000-0003-1022-4326</orcidid><orcidid>https://orcid.org/0000-0003-0748-0863</orcidid><orcidid>https://orcid.org/0000-0003-2790-7393</orcidid><orcidid>https://orcid.org/0000-0002-9226-9917</orcidid><orcidid>https://orcid.org/0000-0001-6586-8335</orcidid><orcidid>https://orcid.org/0000-0003-4807-6250</orcidid></search><sort><creationdate>20220225</creationdate><title>Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses</title><author>Nguyen, Long Chi ; Yang, Dongbo ; Nicolaescu, Vlad ; Best, Thomas J ; Gula, Haley ; Saxena, Divyasha ; Gabbard, Jon D ; Chen, Shao-Nong ; Ohtsuki, Takashi ; Friesen, John Brent ; Drayman, Nir ; Mohamed, Adil ; Dann, Christopher ; Silva, Diane ; Robinson-Mailman, Lydia ; Valdespino, Andrea ; Stock, Letícia ; Suárez, Eva ; Jones, Krysten A ; Azizi, Saara-Anne ; Demarco, Jennifer K ; Severson, William E ; Anderson, Charles D ; Millis, James Michael ; Dickinson, Bryan C ; Tay, Savaş ; Oakes, Scott A ; Pauli, Guido F ; Palmer, Kenneth E ; Meltzer, David O ; Randall, Glenn ; Rosner, Marsha Rich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-5740ba4311311fc30201b2287784baf30757a325ff94cf35a7e13b54f674588f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>A549 Cells</topic><topic>Animals</topic><topic>Antiviral Agents - 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| ispartof | Science advances, 2022-02, Vol.8 (8), p.eabi6110 |
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| language | eng |
| recordid | cdi_crossref_primary_10_1126_sciadv_abi6110 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | A549 Cells Animals Antiviral Agents - chemistry Antiviral Agents - pharmacology Cannabidiol - chemistry Cannabidiol - metabolism Cannabidiol - pharmacology Chlorocebus aethiops COVID-19 - drug therapy COVID-19 - virology Endoplasmic Reticulum Stress - drug effects Endoribonucleases - genetics Endoribonucleases - metabolism Epithelial Cells - virology Female Gene Expression Regulation, Viral - drug effects Host-Pathogen Interactions - drug effects Host-Pathogen Interactions - physiology Humans Immunity, Innate - drug effects Interferons - metabolism Mice Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism SARS-CoV-2 - drug effects SARS-CoV-2 - physiology Vero Cells Virus Internalization - drug effects Virus Replication - drug effects |
| title | Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T05%3A28%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cannabidiol%20inhibits%20SARS-CoV-2%20replication%20through%20induction%20of%20the%20host%20ER%20stress%20and%20innate%20immune%20responses&rft.jtitle=Science%20advances&rft.au=Nguyen,%20Long%20Chi&rft.aucorp=National%20COVID%20Cohort%20Collaborative%20Consortium&rft.date=2022-02-25&rft.volume=8&rft.issue=8&rft.spage=eabi6110&rft.pages=eabi6110-&rft.issn=2375-2548&rft.eissn=2375-2548&rft_id=info:doi/10.1126/sciadv.abi6110&rft_dat=%3Cpubmed_cross%3E35050692%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/35050692&rfr_iscdi=true |