Centers and Institutes
Published January 20, 2022 | Version v1
Journal article Open

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

Creators

  • 1. University of Chicago
  • 2. University of Louisville
  • 3. University of Illinois at Chicago

Description

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.

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Raw and processed RNA-seq data were deposited into the GEO database (GSE168797).

Files

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Additional details

Identifiers

DOI
10.1126/sciadv.abi6110
Other
oai:uchicago.tind.io:10911

Funding

National Institutes of Health
R01 GM121735
National Institutes of Health
R01 CA184494
National Institutes of Health
R01 AI137514
National Institutes of Health
R01 AI127518
National Institutes of Health
R01 AI134980
National Institutes of Health
R01 CA219815
National Institutes of Health
R35 GM119840
National Institutes of Health
P30 CA014599
University of Chicago
BIG Vision Grant

UChicago Information

Division(s)
Biological Sciences Division, Physical Sciences Division, Pritzker School of Molecular Engineering
Department(s)
Ben May Department for Cancer Research, Chemistry, Microbiology, Pathology, Surgery
Center(s) or Institute(s)
Center for Health and the Social Sciences