Author:
Malone Robert W.,Tisdall Philip,Fremont-Smith Philip,Liu Yongfeng,Huang Xi-Ping,White Kris M.,Miorin Lisa,Moreno Elena,Alon Assaf,Delaforge Elise,Hennecker Christopher D.,Wang Guanyu,Pottel Joshua,Blair Robert V.,Roy Chad J.,Smith Nora,Hall Julie M.,Tomera Kevin M,Shapiro Gideon,Mittermaier Anthony,Kruse Andrew C.,García-Sastre Adolfo,Roth Bryan L.,Glasspool-Malone Jill,Ricke Darrell O.
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.
Funder
U.S. Air Force
Defense Advanced Research Projects Agency
National Institutes of Health
Office of Extramural Research, National Institutes of Health
U.S. Department of Defense
Subject
Pharmacology (medical),Pharmacology
Cited by
65 articles.
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