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

Overview

Journal bioRxiv

Date 2021 Mar 24

PMID 33758843

Citations 1

Authors

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

Savas Tay

Scott A Oakes

Guido F Pauli

David O Meltzer

Glenn Randall

Marsha Rich Rosner

Affiliations

Soon will be listed here.

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.

Citing Articles

The Prevalence of Dietary Supplement Use for the Purpose of COVID-19 Prevention in Japan.

Chiba T, Tanemura N Nutrients. 2022; 14(15).

PMID: 35956391 PMC: 9370294. DOI: 10.3390/nu14153215.

References

Wang R, Simoneau C, Kulsuptrakul J, Bouhaddou M, Travisano K, Hayashi J . Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses. Cell. 2020; 184(1):106-119.e14. PMC: 7723770. DOI: 10.1016/j.cell.2020.12.004. View

Marker D, Tremblay M, Puccini J, Barbieri J, Gantz Marker M, Loweth C . The new small-molecule mixed-lineage kinase 3 inhibitor URMC-099 is neuroprotective and anti-inflammatory in models of human immunodeficiency virus-associated neurocognitive disorders. J Neurosci. 2013; 33(24):9998-10010. PMC: 3682381. DOI: 10.1523/JNEUROSCI.0598-13.2013. View

Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I . Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A. 2020; 117(13):7001-7003. PMC: 7132130. DOI: 10.1073/pnas.2002589117. View

Kneller D, Phillips G, ONeill H, Jedrzejczak R, Stols L, Langan P . Structural plasticity of SARS-CoV-2 3CL M active site cavity revealed by room temperature X-ray crystallography. Nat Commun. 2020; 11(1):3202. PMC: 7314768. DOI: 10.1038/s41467-020-16954-7. View

Daniloski Z, Jordan T, Wessels H, Hoagland D, Kasela S, Legut M . Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells. Cell. 2020; 184(1):92-105.e16. PMC: 7584921. DOI: 10.1016/j.cell.2020.10.030. View

Weiss S, Leibowitz J . Coronavirus pathogenesis. Adv Virus Res. 2011; 81:85-164. PMC: 7149603. DOI: 10.1016/B978-0-12-385885-6.00009-2. View

Jaimes J, Millet J, Whittaker G . Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site. iScience. 2020; 23(6):101212. PMC: 7255728. DOI: 10.1016/j.isci.2020.101212. View

Blanco-Melo D, Nilsson-Payant B, Liu W, Uhl S, Hoagland D, Moller R . Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020; 181(5):1036-1045.e9. PMC: 7227586. DOI: 10.1016/j.cell.2020.04.026. View

Galloway S, Paul P, MacCannell D, Johansson M, Brooks J, MacNeil A . Emergence of SARS-CoV-2 B.1.1.7 Lineage - United States, December 29, 2020-January 12, 2021. MMWR Morb Mortal Wkly Rep. 2021; 70(3):95-99. PMC: 7821772. DOI: 10.15585/mmwr.mm7003e2. View

10.

Osipiuk J, Azizi S, Dvorkin S, Endres M, Jedrzejczak R, Jones K . Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors. Nat Commun. 2021; 12(1):743. PMC: 7854729. DOI: 10.1038/s41467-021-21060-3. View

11.

Anil S, Shalev N, Vinayaka A, Nadarajan S, Namdar D, Belausov E . Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages. Sci Rep. 2021; 11(1):1462. PMC: 7809280. DOI: 10.1038/s41598-021-81049-2. View

12.

Muthumalage T, Rahman I . Cannabidiol differentially regulates basal and LPS-induced inflammatory responses in macrophages, lung epithelial cells, and fibroblasts. Toxicol Appl Pharmacol. 2019; 382:114713. PMC: 6917034. DOI: 10.1016/j.taap.2019.114713. View

13.

Zhou Q, Chen V, Shannon C, Wei X, Xiang X, Wang X . Interferon-α2b Treatment for COVID-19. Front Immunol. 2020; 11:1061. PMC: 7242746. DOI: 10.3389/fimmu.2020.01061. View

14.

Nelson K, Bisson J, Singh G, Graham J, Chen S, Friesen J . The Essential Medicinal Chemistry of Cannabidiol (CBD). J Med Chem. 2020; 63(21):12137-12155. PMC: 7666069. DOI: 10.1021/acs.jmedchem.0c00724. View

15.

Abu Aboud O, Chen C, Senapedis W, Baloglu E, Argueta C, Weiss R . Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth. Mol Cancer Ther. 2016; 15(9):2119-29. PMC: 5010932. DOI: 10.1158/1535-7163.MCT-16-0197. View

16.

Schneider W, Luna J, Hoffmann H, Sanchez-Rivera F, Leal A, Ashbrook A . Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks. Cell. 2020; 184(1):120-132.e14. PMC: 7796900. DOI: 10.1016/j.cell.2020.12.006. View

17.

Haller O, Kochs G, Weber F . The interferon response circuit: induction and suppression by pathogenic viruses. Virology. 2005; 344(1):119-30. PMC: 7125643. DOI: 10.1016/j.virol.2005.09.024. View

18.

Sorkin B, Kuszak A, Bloss G, Fukagawa N, Hoffman F, Jafari M . Improving natural product research translation: From source to clinical trial. FASEB J. 2020; 34(1):41-65. PMC: 7470648. DOI: 10.1096/fj.201902143R. View

19.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

20.

OLeary N, Wright M, Brister J, Ciufo S, Haddad D, McVeigh R . Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 2015; 44(D1):D733-45. PMC: 4702849. DOI: 10.1093/nar/gkv1189. View