Cannabigerol and Cannabicyclol Block SARS-CoV-2 Cell Fusion

Nica Classen; Thanet Pitakbut; Michael Schöfbänker; Joachim Kühn; Eike R. Hrincius; Stephan Ludwig; Andreas Hensel; Oliver Kayser

doi:10.1055/a-2320-8822

Planta Medica, Table of Contents

Planta Med 2024; 90(09): 717-725
DOI: 10.1055/a-2320-8822

Biological and Pharmacological Activity

Original Papers

Cannabigerol and Cannabicyclol Block SARS-CoV-2 Cell Fusion

Nica Classen

²Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany

,

Thanet Pitakbut

¹Technical Biochemistry Laboratory, Faculty of Biochemical and Chemical Engineering, Technical University of Dortmund, Germany

,

Michael Schöfbänker

³Institute of Virology Münster (IVM), University of Münster, Germany

,

Joachim Kühn

³Institute of Virology Münster (IVM), University of Münster, Germany

,

Eike R. Hrincius

³Institute of Virology Münster (IVM), University of Münster, Germany

,

Stephan Ludwig

³Institute of Virology Münster (IVM), University of Münster, Germany

,

Andreas Hensel

²Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany

,

Oliver Kayser

¹Technical Biochemistry Laboratory, Faculty of Biochemical and Chemical Engineering, Technical University of Dortmund, Germany

› Author Affiliations

Abstract

The search for new active substances against SARS-CoV-2 is still a central challenge after the COVID-19 pandemic. Antiviral agents to complement vaccination are an important pillar in the clinical situation. Selected cannabinoids such as cannabigerol, cannabicyclol, cannabichromene, and cannabicitran from Cannabis sativa and synthetic homologues of cannabigerol and cannabicyclol were evaluated for effects on the cell viability of Vero cells (CC₅₀ of cannabigerol and cannabicyclol 40 resp. 38 µM) and reduced virus entry of vesicular stomatitis pseudotyped viruses with surface-expressed SARS-CoV-2 spike protein at 20 µM. In addition to a reduction of pseudotyped virus entry, a titer reduction assay on Vero cells after preincubation of Wuhan SARS-CoV-2 significantly confirmed antiviral activity. Investigations on the molecular targets addressed by cannabigerol and cannabicyclol indicated that both compounds are inhibitors of SARS-CoV-2 spike protein-mediated membrane fusion, as could be shown by a virus-free reporter fusion inhibition assay (EC₅₀ for cannabigerol 5.5 µM and for cannabicyclol 10.8 µM) and by monitoring syncytia formation in Vero reporter cells. Selectivity indices were calculated as 7.4 for cannabigerol and 3.5 for cannabicyclol. Systematic semisynthetic alterations of cannabigerol and cannabicyclol indicated that the side chains of both compounds do not contribute to the observed anti-membrane fusion activity.

Keywords

COVID-19 - SARS-CoV-2 - Cannabis sativa - Cannabaceae - cannabinoids - cannabigerol - cannabicyclol - membrane fusion - virulence factors

Full Text

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