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.
Copyright © 2021 Malone, Tisdall, Fremont-Smith, Liu, Huang, White, Miorin, Moreno, Alon, Delaforge, Hennecker, Wang, Pottel, Blair, Roy, Smith, Hall, Tomera, Shapiro, Mittermaier, Kruse, García-Sastre, Roth, Glasspool-Malone and Ricke.