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

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.
AuthorsRichard B van Breemen, Ruth N Muchiri, Timothy A Bates, Jules B Weinstein, Hans C Leier, Scotland Farley, Fikadu G Tafesse
JournalJournal of natural products (J Nat Prod) Vol. 85 Issue 1 Pg. 176-184 (01 28 2022) ISSN: 1520-6025 [Electronic] United States
PMID35007072 (Publication Type: Journal Article)
Chemical References
  • Antiviral Agents
  • Benzoates
  • Cannabinoids
  • Ligands
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • cannabigerolic acid
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • cannabidiolic acid
Topics
  • Angiotensin-Converting Enzyme 2 (metabolism)
  • Animals
  • Antiviral Agents (chemistry, metabolism, pharmacology)
  • Benzoates (pharmacology)
  • COVID-19 (prevention & control)
  • Cannabinoids (chemistry, metabolism, 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)
  • COVID-19 Drug Treatment

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