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

Robert W. Malone, Philip Tisdall, Philip Fremont-Smith, Yongfeng Liu, Xi Ping Huang, Kris M. White, Lisa Miorin, Elena Moreno, Assaf Alon, Elise Delaforge, Christopher D. Hennecker, Guanyu Wang, Joshua Pottel, Robert V. Blair, Chad J. Roy, Nora Smith, Julie M. Hall, Kevin M. Tomera, Gideon Shapiro, Anthony MittermaierAndrew C. Kruse, Adolfo García-Sastre, Bryan L. Roth, Jill Glasspool-Malone, Darrell O. Ricke

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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.

Original languageEnglish
Article number633680
JournalFrontiers in Pharmacology
StatePublished - 23 Mar 2021


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


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