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Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response

Long Chi Nguyen, View ORCID ProfileDongbo Yang, Vlad Nicolaescu, Thomas J. Best, Takashi Ohtsuki, Shao-Nong Chen, J. Brent Friesen, View ORCID ProfileNir Drayman, Adil Mohamed, View ORCID ProfileChristopher Dann, Diane Silva, Haley Gula, View ORCID ProfileKrysten A. Jones, View ORCID ProfileJ. Michael Millis, View ORCID ProfileBryan C. Dickinson, Savaş Tay, Scott A. Oakes, View ORCID ProfileGuido F. Pauli, View ORCID ProfileDavid O. Meltzer, View ORCID ProfileGlenn Randall, View ORCID ProfileMarsha Rich Rosner
doi: https://doi.org/10.1101/2021.03.10.432967
Long Chi Nguyen
1Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637
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Dongbo Yang
1Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637
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Vlad Nicolaescu
2Department of Microbiology, University of Chicago, Chicago, IL 60637
9Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont IL 60439
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Thomas J. Best
3Center for Health and the Social Sciences, University of Chicago, Chicago IL 60637
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Takashi Ohtsuki
4College of Pharmacy, Pharmacognosy Institute, University of Illinois at Chicago, Chicago IL 60612
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Shao-Nong Chen
4College of Pharmacy, Pharmacognosy Institute, University of Illinois at Chicago, Chicago IL 60612
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J. Brent Friesen
4College of Pharmacy, Pharmacognosy Institute, University of Illinois at Chicago, Chicago IL 60612
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Nir Drayman
6Pritzker School of Molecular Engineering, University of Chicago, Chicago IL 60637
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Adil Mohamed
6Pritzker School of Molecular Engineering, University of Chicago, Chicago IL 60637
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Christopher Dann
1Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637
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Diane Silva
5Department of Pathology, University of Chicago, Chicago IL 60637
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Haley Gula
2Department of Microbiology, University of Chicago, Chicago, IL 60637
9Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont IL 60439
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Krysten A. Jones
7Department of Chemistry, University of Chicago, Chicago IL 60637
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J. Michael Millis
8Department of Surgery, University of Chicago, Chicago IL 60637
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Bryan C. Dickinson
7Department of Chemistry, University of Chicago, Chicago IL 60637
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Savaş Tay
6Pritzker School of Molecular Engineering, University of Chicago, Chicago IL 60637
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Scott A. Oakes
5Department of Pathology, University of Chicago, Chicago IL 60637
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Guido F. Pauli
4College of Pharmacy, Pharmacognosy Institute, University of Illinois at Chicago, Chicago IL 60612
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David O. Meltzer
3Center for Health and the Social Sciences, University of Chicago, Chicago IL 60637
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Glenn Randall
2Department of Microbiology, University of Chicago, Chicago, IL 60637
9Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont IL 60439
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  • For correspondence: grandall@bsd.uchicago.edu mrosner@uchicago.edu
Marsha Rich Rosner
1Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637
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  • For correspondence: grandall@bsd.uchicago.edu mrosner@uchicago.edu
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ABSTRACT

The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.

Competing Interest Statement

Five of the authors (MRR, GR, LCN, DY and JMM) filed a provisional patent entitled Method of use of Cannabidiol as an antiviral agent. Receipt of the provisional patient was acknowledged by the USPTO on November 30, 2020. S.A.O. is a cofounder and consultant at OptiKira., L.L.C. (Cleveland, OH).

Footnotes

  • ↵^ Current affiliation: Department of Food Bioscience and Biotechnology, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan

  • Summary sentence: Cannabidiol from the cannabis plant has potential to prevent and inhibit SARS-CoV-2 infection

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 10, 2021.
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Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response
Long Chi Nguyen, Dongbo Yang, Vlad Nicolaescu, Thomas J. Best, Takashi Ohtsuki, Shao-Nong Chen, J. Brent Friesen, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Haley Gula, Krysten A. Jones, J. Michael Millis, Bryan C. Dickinson, Savaş Tay, Scott A. Oakes, Guido F. Pauli, David O. Meltzer, Glenn Randall, Marsha Rich Rosner
bioRxiv 2021.03.10.432967; doi: https://doi.org/10.1101/2021.03.10.432967
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Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response
Long Chi Nguyen, Dongbo Yang, Vlad Nicolaescu, Thomas J. Best, Takashi Ohtsuki, Shao-Nong Chen, J. Brent Friesen, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Haley Gula, Krysten A. Jones, J. Michael Millis, Bryan C. Dickinson, Savaş Tay, Scott A. Oakes, Guido F. Pauli, David O. Meltzer, Glenn Randall, Marsha Rich Rosner
bioRxiv 2021.03.10.432967; doi: https://doi.org/10.1101/2021.03.10.432967

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