Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants

J Nat Prod. 2022 Jan 28;85(1):176-184. doi: 10.1021/acs.jnatprod.1c00946. Epub 2022 Jan 10.

Abstract

As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection-mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Benzoates / pharmacology
  • COVID-19 / drug therapy*
  • COVID-19 / prevention & control
  • Cannabinoids / chemistry
  • Cannabinoids / metabolism
  • Cannabinoids / pharmacology*
  • Chlorocebus aethiops
  • Humans
  • Ligands
  • Mass Spectrometry
  • Models, Molecular
  • Protein Binding
  • SARS-CoV-2 / drug effects*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells
  • Virus Internalization / drug effects*

Substances

  • Antiviral Agents
  • Benzoates
  • Cannabinoids
  • Ligands
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • cannabigerolic acid
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • cannabidiolic acid

Supplementary concepts

  • SARS-CoV-2 variants