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
RW Malone MD LLC, Madison, VA, United States.
Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute, New York, NY, United States.
Front Pharmacol. 2021 Mar 23;12:633680. doi: 10.3389/fphar.2021.633680. eCollection 2021.
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 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.
新冠病毒感染是导致新冠肺炎的必要条件，但新冠肺炎的许多体征和症状与常见急性病毒性疾病不同。新冠病毒感染是临床新冠肺炎发病的必要条件，但并非充分条件。目前，尚无获批的新冠肺炎暴露前或暴露后预防性医学应对措施。临床数据表明，法莫替丁可能减轻新冠肺炎病情，但其作用机制和剂量选择依据仍不明确。我们研究了法莫替丁活性的几种合理假设，包括抗病毒和宿主介导的作用机制。我们提出，法莫替丁缓解新冠肺炎症状的主要作用机制涉及靶向组胺受体H活性，且临床新冠肺炎的发病涉及肥大细胞功能失调和组胺释放。基于这些发现及相关假设，正在研发并临床测试基于重新利用特性明确药物的新型新冠肺炎多药治疗策略，其中许多药物在全球范围内都有价格低廉的通用口服剂型，适用于新冠肺炎疾病的门诊和住院治疗。
