Frontiers in Pharmacology (Mar 2021)
COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms
- Robert W. Malone,
- Robert W. Malone,
- Philip Tisdall,
- Philip Fremont-Smith,
- Yongfeng Liu,
- Xi-Ping Huang,
- Kris M. White,
- Kris M. White,
- Lisa Miorin,
- Lisa Miorin,
- Elena Moreno,
- Elena Moreno,
- Assaf Alon,
- Elise Delaforge,
- Christopher D. Hennecker,
- Guanyu Wang,
- Joshua Pottel,
- Robert V. Blair,
- Robert V. Blair,
- Chad J. Roy,
- Chad J. Roy,
- Nora Smith,
- Julie M. Hall,
- Kevin M Tomera,
- Gideon Shapiro,
- Anthony Mittermaier,
- Andrew C. Kruse,
- Adolfo García-Sastre,
- Adolfo García-Sastre,
- Adolfo García-Sastre,
- Adolfo García-Sastre,
- Bryan L. Roth,
- Jill Glasspool-Malone,
- Darrell O. Ricke
Affiliations
- Robert W. Malone
- RW Malone MD LLC, Madison, VA, United States
- Robert W. Malone
- 7Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute, New York, NY, United States
- Philip Tisdall
- Medical School Companion LLC, Marco Island, FL, United States
- Philip Fremont-Smith
- MIT Lincoln Laboratory, Lexington, MA, United States
- Yongfeng Liu
- Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States
- Xi-Ping Huang
- Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States
- Kris M. White
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Kris M. White
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Lisa Miorin
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Lisa Miorin
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Elena Moreno
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Elena Moreno
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Assaf Alon
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, United States
- Elise Delaforge
- Department of Chemistry, McGill University, Montreal, QC, Canada
- Christopher D. Hennecker
- Department of Chemistry, McGill University, Montreal, QC, Canada
- Guanyu Wang
- Department of Chemistry, McGill University, Montreal, QC, Canada
- Joshua Pottel
- Molecular Forecaster Inc, Montreal, QC, Canada
- Robert V. Blair
- 0Tulane National Primate Research Center, Covington, LA, United Sates
- Robert V. Blair
- 1Department of Pathology and Laboratory Animal Medicine, Tulane University School of Medicine, New Orleans, LA, United States
- Chad J. Roy
- 0Tulane National Primate Research Center, Covington, LA, United Sates
- Chad J. Roy
- 2Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, United States
- Nora Smith
- MIT Lincoln Laboratory, Lexington, MA, United States
- Julie M. Hall
- 3Frank H. Netter MD School of Medicine – Quinnipiac University, Hamden, CT, United States
- Kevin M Tomera
- 4Department of Urology, Beloit Memorial Hospital, Beloit, WI, United States
- Gideon Shapiro
- 5Pharmorx LLC, Gainesville, FL, United States
- Anthony Mittermaier
- Department of Chemistry, McGill University, Montreal, QC, Canada
- Andrew C. Kruse
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, United States
- Adolfo García-Sastre
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Adolfo García-Sastre
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Adolfo García-Sastre
- 6Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Adolfo García-Sastre
- 7Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute, New York, NY, United States
- Bryan L. Roth
- Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States
- Jill Glasspool-Malone
- RW Malone MD LLC, Madison, VA, United States
- Darrell O. Ricke
- MIT Lincoln Laboratory, Lexington, MA, United States
- DOI
- https://doi.org/10.3389/fphar.2021.633680
- Journal volume & issue
-
Vol. 12
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
- famotidine (PubChem CID: 3325)
- mast cell activating disorder
- COVID-19
- hyperinflammation state
- GPCR (G Protein Coupled Receptors)
- histamine (H2) receptor
