Cannabigerol and Cannabicyclol Block SARS-CoV-2 Cell Fusion

Area of Science:

• Virology
• Pharmacology
• Biochemistry

Background:

• The ongoing search for effective SARS-CoV-2 treatments remains critical post-pandemic.
• Antiviral therapies are essential complements to vaccination strategies for managing COVID-19.
• Cannabinoids from Cannabis sativa and synthetic analogues are being investigated for their therapeutic potential.

Purpose of the Study:

• To evaluate the antiviral effects of selected cannabinoids against SARS-CoV-2.
• To determine the mechanism of action, focusing on viral entry and membrane fusion inhibition.
• To assess the therapeutic potential of cannabinoids as adjuncts to COVID-19 vaccination.

Main Methods:

• Assessed cell viability (CC50) of Vero cells treated with cannabinoids.
• Evaluated reduction in pseudotyped virus entry and SARS-CoV-2 titer reduction.
• Investigated inhibition of SARS-CoV-2 spike protein-mediated membrane fusion using reporter assays and syncytia formation monitoring.

Main Results:

• Cannabigerol and cannabicyclol demonstrated antiviral activity by reducing pseudotyped virus entry and SARS-CoV-2 titers.
• Both compounds were identified as inhibitors of SARS-CoV-2 spike protein-mediated membrane fusion, with specific EC50 values.
• Selectivity indices indicated a favorable safety profile for further investigation.

Conclusions:

• Cannabigerol and cannabicyclol exhibit significant antiviral properties against SARS-CoV-2, primarily through inhibiting membrane fusion.
• The side chains of these cannabinoids do not appear essential for their anti-membrane fusion activity.
• These findings highlight the potential of cannabinoids as novel therapeutic agents for COVID-19 treatment.