Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses-Reference-Cited by-同舟云学术

Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses

Published:2022-02-25 Issue:8 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Nguyen Long Chi¹^ORCID,Yang Dongbo¹^ORCID,Nicolaescu Vlad²³^ORCID,Best Thomas J.⁴^ORCID,Gula Haley²³^ORCID,Saxena Divyasha⁵,Gabbard Jon D.⁵,Chen Shao-Nong⁶^ORCID,Ohtsuki Takashi⁶,Friesen John Brent⁶^ORCID,Drayman Nir⁷^ORCID,Mohamed Adil⁷,Dann Christopher¹,Silva Diane⁸,Robinson-Mailman Lydia¹,Valdespino Andrea¹,Stock Letícia¹^ORCID,Suárez Eva¹,Jones Krysten A.⁹^ORCID,Azizi Saara-Anne⁹^ORCID,Demarco Jennifer K.⁵^ORCID,Severson William E.⁵,Anderson Charles D.⁵,Millis James Michael¹⁰^ORCID,Dickinson Bryan C.⁹^ORCID,Tay Savaş⁷^ORCID,Oakes Scott A.⁸^ORCID,Pauli Guido F.⁶^ORCID,Palmer Kenneth E.⁵^ORCID,Meltzer David O.⁴^ORCID,Randall Glenn²³^ORCID,Rosner Marsha Rich¹^ORCID,

Affiliation:

1. Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.

2. Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.

3. Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont, IL 60439, USA.

4. Center for Health and the Social Sciences, University of Chicago, Chicago, IL 60637, USA.

5. Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40222, USA.

6. Pharmacognosy Institute and Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.

7. Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.

8. Department of Pathology, University of Chicago, Chicago, IL 60637, USA.

9. Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.

10. Department of Surgery, University of Chicago, Chicago, IL 60637, USA.

Abstract

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ongoing coronavirus disease 2019 (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 ribonuclease 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 current use of non-medical formulations as a preventative or treatment therapy.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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