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 Mittermaier, Andrew C Kruse, Adolfo García-Sastre, Bryan L Roth, Jill Glasspool-Malone, Darrell O Ricke
Frontiers in Pharmacology, doi:10.3389/fphar.2021.633680
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 H 2 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.
ETHICS STATEMENT Ethical review and approval was not required for the study on human participants in accordance with the local legislation and the institutional requirements. The patients/participants provided their written informed consent to participate in this study. The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of Tulane University. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
AUTHOR CONTRIBUTIONS Primary research design and data were generated by YL, X-PH, KW, LM, EM, AA, ED, GW., RB, CR, Modeling, data interpretation, analysis/theory development, experimental design guidance, figure and manuscript authorship were primarily performed by RM, PT, CH, PF-S, JP, RB, CR, NS, JH, KT, GS, AM, AK, AS, BR, JG-M, and DR. Conflict of Interest: RM, PT, and GS were employed by the companies RW Malone MD LLC, Medical School Companion LLC, and Pharmorx LLC, respectively. In all three cases, their contributions to the work described were voluntary and uncompensated. By joint agreement, no patent rights relating to these findings have been asserted by any of the authors. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Copyright © 2021 Malone, Tisdall, Fremont-Smith, Liu, Huang, White, Miorin,..
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'abstract': '<jats:p>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 H<jats:sub>2</jats:sub> 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.</jats:p>',
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'journal-title': 'Front Oncol.'}],
'container-title': 'Frontiers in Pharmacology',
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'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fphar.2021.633680/full',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 3, 23]],
'date-time': '2021-03-23T06:50:37Z',
'timestamp': 1616482237000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fphar.2021.633680/full'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 3, 23]]},
'references-count': 129,
'alternative-id': ['10.3389/fphar.2021.633680'],
'URL': 'http://dx.doi.org/10.3389/fphar.2021.633680',
'relation': {},
'ISSN': ['1663-9812'],
'subject': [],
'container-title-short': 'Front. Pharmacol.',
'published': {'date-parts': [[2021, 3, 23]]}}
