COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms

  • Front Pharmacol. 2021 Mar 23:12:633680. doi: 10.3389/fphar.2021.633680.
Robert W Malone  1  2 ,  Philip Tisdall  3 ,  Philip Fremont-Smith  4 ,  Yongfeng Liu  5 ,  Xi-Ping Huang  5 ,  Kris M White  6  7 ,  Lisa Miorin  6  7 ,  Elena Moreno  6  7 ,  Assaf Alon  8 ,  Elise Delaforge  9 ,  Christopher D Hennecker  9 ,  Guanyu Wang  9 ,  Joshua Pottel  10 ,  Robert V Blair  11  12 ,  Chad J Roy  11  13 ,  Nora Smith  4 ,  Julie M Hall  14 ,  Kevin M Tomera  15 ,  Gideon Shapiro  16 ,  Anthony Mittermaier  9 ,  Andrew C Kruse  8 ,  Adolfo García-Sastre  6  7  17  2 ,  Bryan L Roth  5 ,  Jill Glasspool-Malone  1 ,  Darrell O Ricke  4
Affiliations
  • 1. RW Malone MD LLC, Madison, VA, United States.
  • 2. Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute, New York, NY, United States.
  • 3. Medical School Companion LLC, Marco Island, FL, United States.
  • 4. MIT Lincoln Laboratory, Lexington, MA, United States.
  • 5. Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States.
  • 6. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
  • 7. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
  • 8. Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, United States.
  • 9. Department of Chemistry, McGill University, Montreal, QC, Canada.
  • 10. Molecular Forecaster Inc, Montreal, QC, Canada.
  • 11. Tulane National Primate Research Center, Covington, LA, United Sates.
  • 12. Department of Pathology and Laboratory Animal Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
  • 13. Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, United States.
  • 14. Frank H. Netter MD School of Medicine - Quinnipiac University, Hamden, CT, United States.
  • 15. Department of Urology, Beloit Memorial Hospital, Beloit, WI, United States.
  • 16. Pharmorx LLC, Gainesville, FL, United States.
  • 17. Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
PMID: 33833683 DOI: 10.3389/fphar.2021.633680
Abstract

SARS-CoV-2 Infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 Infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We have investigated several plausible hypotheses for famotidine activity including Antiviral and host-mediated mechanisms of action. We propose that the principal mechanism of action of famotidine for relieving COVID-19 symptoms involves on-target Histamine Receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release. Based on these findings and associated hypothesis, new COVID-19 multi-drug treatment strategies based on repurposing well-characterized drugs are being developed and clinically tested, and many of these drugs are available worldwide in inexpensive generic oral forms suitable for both outpatient and inpatient treatment of COVID-19 disease.

Keywords
COVID-19; GPCR (G Protein Coupled Receptors); famotidine (PubChem CID: 3325); histamine (H2) receptor; hyperinflammation state; mast cell activating disorder.
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