Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses.
Long Chi NguyenDongbo YangVlad NicolaescuThomas J BestHaley GulaDivyasha SaxenaJon D GabbardShao-Nong ChenTakashi OhtsukiJohn Brent FriesenNir DraymanAdil MohamedChristopher DannDiane SilvaLydia Robinson-MailmanAndrea ValdespinoLetícia StockEva SuárezKrysten A JonesSaara-Anne AziziJennifer K DemarcoWilliam E SeversonCharles D AndersonJames Michael MillisBryan C DickinsonSavaÅŸ TayScott A OakesGuido F PauliKenneth E PalmerChristopher G ChuteDavid O MeltzerGlenn RandallMarsha Rich RosnerPublished in: Science advances (2022)
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 IRE1α 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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- immune response
- gene expression
- early stage
- clinical trial
- endoplasmic reticulum
- end stage renal disease
- signaling pathway
- chronic kidney disease
- induced apoptosis
- dna methylation
- endothelial cells
- squamous cell carcinoma
- peritoneal dialysis
- dendritic cells
- quality improvement
- cell proliferation
- prognostic factors
- epithelial mesenchymal transition
- risk assessment
- cell death
- mesenchymal stem cells
- skeletal muscle
- climate change
- neoadjuvant chemotherapy
- high fat diet induced
- metabolic syndrome
- pi k akt
- double blind
- study protocol