Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
Long Chi Nguyen, Dongbo Yang, Vlad Nicolaescu, Thomas J Best, Haley Gula, Divyasha Saxena, Jon D Gabbard, Shao-Nong Chen, Takashi Ohtsuki, John Brent Friesen, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Lydia Robinson-Mailman, Andrea Valdespino, Letícia Stock, Eva Suárez, Krysten A Jones, Saara-Anne Azizi, Jennifer K Demarco, William E Severson, Charles D Anderson, James Michael Millis, Bryan C Dickinson, Savaş Tay, Scott A Oakes, Guido F Pauli, Kenneth E Palmer, The National COVID Cohort Collaborative Consortium, David O Meltzer, Glenn Randall, Marsha Rich Rosner
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 IRE1 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.
SUPPLEMENTARY MATERIALS Supplementary material for this article is available at https://science.org/doi/10.1126/ sciadv.abi6110 View/request a protocol for this paper from Bio-protocol. Teaser: Cannabidiol from the cannabis plant has potential to prevent and inhibit SARS-CoV-2 infection.
of 18 National COVID Cohort Collaborative (N3C). The patient data analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave covid.cd2h.org/enclave and supported by NCATS U24 TR002306. This research was possible because of the patients whose information is included within the data from participating organizations (covid.cd2h.org/dtas) and the organizations (https://ncats.nih.gov/n3c/ resources/data-contribution/data-transfer-agreement-signatories) and scientists who have contributed to the on-going development of this community resource (28) . The project described was supported by the National Institute of General Medical Sciences, 5U54GM104942-04. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The analysis used only de-identified data (i.e., N3C Data Access Tier 2, described at https://covid.cd2h.org/N3C_governance). We gratefully acknowledge contributions from the following N3C core teams:
of 18 • Additional N3C acknowledgments. We would also like to thank others not listed above: Joy Alamgir (ARIScience), Seth Russell, MS (University of Colorado),..
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