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

Long Chi Nguyen | Zendy; Dongbo Yang | Zendy; Vlad Nicolaescu | Zendy; Thomas J. Best | Zendy; Haley Gula | Zendy; Divyasha Saxena | Zendy; Jon D. Gabbard | Zendy; Shaog Chen | Zendy; Takashi Ohtsuki | Zendy; J. Brent Friesen | Zendy; Nir Drayman | Zendy; Adil Mohamed | Zendy; Christopher Dann | Zendy; Diane Silva | Zendy; Lydia Robinson-Mailman | Zendy; Andrea Valdespino | Zendy; Letícia Stock | Zendy; Eva Amanda del Pilar Gallego Suárez | Zendy; Krysten A. Jones | Zendy; SaaraAnne Azizi | Zendy; Jennifer K. DeMarco | Zendy; William E. Severson | Zendy; Charles D. Anderson | Zendy; James Michael Millis | Zendy; Bryan C. Dickinson | Zendy; Savaş Tay | Zendy; Scott A. Oakes | Zendy; Guido F. Pauli | Zendy; Kenneth E. Palmer | Zendy; David O. Meltzer | Zendy; Glenn Randall | Zendy; Marsha Rich Rosner | Zendy

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

Author(s) -

Long Chi Nguyen,

Dongbo Yang,

Vlad Nicolaescu,

Thomas J. Best,

Haley Gula,

Divyasha Saxena,

Jon D. Gabbard,

Shaog Chen,

Takashi Ohtsuki,

J. Brent Friesen,

Nir Drayman,

Adil Mohamed,

Christopher Dann,

Diane Silva,

Lydia Robinson-Mailman,

Andrea Valdespino,

Letícia Stock,

Eva Amanda del Pilar Gallego Suárez,

Krysten A. Jones,

SaaraAnne 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,

David O. Meltzer,

Glenn Randall,

Marsha Rich Rosner

Publication year - 2022

Publication title -

science advances

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.928

H-Index - 146

ISSN - 2375-2548

DOI - 10.1126/sciadv.abi6110

Subject(s) - viral replication , cannabidiol , innate immune system , medicine , virology , immune system , immunology , interferon , biology , virus , cannabis , psychiatry

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.

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