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 Del Olmo; Assaf Alon; Elise Delaforge; Christopher D Hennecker; Guanyu Wang; Joshua Pottel; Nora Smith; Julie M Hall; Gideon Shapiro; Anthony Mittermaier; Andrew C Kruse; Adolfo García-Sastre; Bryan L Roth; Jill Glasspool-Malone; Darrell O Ricke

doi:10.21203/rs.3.rs-30934/v2

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

Res Sq [Preprint]. 2020 Aug 31:rs.3.rs-30934. doi: 10.21203/rs.3.rs-30934/v2.

Authors

Robert W Malone¹, Philip Tisdall², Philip Fremont-Smith³, Yongfeng Liu⁴, Xi-Ping Huang⁴, Kris M White⁵, Lisa Miorin⁶, Elena Moreno Del Olmo⁶, Assaf Alon⁷, Elise Delaforge⁸, Christopher D Hennecker⁸, Guanyu Wang⁸, Joshua Pottel⁹, Nora Smith³, Julie M Hall¹⁰, Gideon Shapiro¹¹, Anthony Mittermaier⁸, Andrew C Kruse⁷, Adolfo García-Sastre¹², Bryan L Roth⁴, Jill Glasspool-Malone¹, Darrell O Ricke³

Affiliations

¹ RW Malone MD LLC, Madison, VA.
² Medical School Companion LLC, Marco Island, FL.
³ MIT Lincoln Laboratory, Lexington, MA.
⁴ Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, NC.
⁵ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.
⁶ Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
⁷ Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA.
⁸ McGill University, Department of Chemistry, Montreal, Quebec, Canada.
⁹ Molecular Forecaster Inc, Montreal, Quebec, Canada.
¹⁰ Frank H. Netter MD School of Medicine - Quinnipiac University, Hamden, CT.
¹¹ Pharmorx LLC, Gainesville, FL.
¹² Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY,Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Abstract

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no 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 explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H₂ activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.

Keywords: COVID-19; Famotidine; GPCR; Histamine; Mast Cell.

Publication types

Preprint

Abstract

Publication types

Grants and funding