Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis

Introduction Famotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19. Methods Five databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated. Results Four studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death—HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%. Conclusion Based on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

Famotidine promotes inflammation by triggering cell pyroptosis in gastric cancer cells

Background Cell pyroptosis has been characterized by cell swelling and pro-inflammatory factors release to aggravate inflammatory reaction., such as interlukin-1 beta (IL-1β) and interlukin18 (IL-18). However, the function of famotidine, an antagonist of histamine H2-receptor antagonists, in cell pyroptosis remained unknown. Methods Real-time quantitative PCR (qPCR), western blotting (WB), LDH release assay and enzyme linked immunosorbent assay (Elisa) combined with inhibitor were performed to analyze the effect of famotidine on cell pyroptosis-related gene expression. Results In this study, we found that famotidine (300 μm) treatment led to a phenomenon of cell pyroptosis as confirmed by LDH assay. Further results showed that famotidine triggered cell pyroptosis in gastric cancer cells by activation of NLPR3 inflammasomes including ASC, Caspase-1 and NLRP, leading to enhanced IL-18, not IL-1β, mature and secretion. What’s more, the results also showed GSDME, not GSDMD, was increased in response to famotidine stimulation in BGC823 and AGS cells. Mechanically, phosphorylation of ERK1/2 was drastically enhanced in present with famotidine treatment, while inhibition of ERK1/2 activity by U0126 could reverse the promotion of famotidine in IL-18 secretion. Conclusion These findings revealed a novel role of famotidine in cell pyroptosis in patients with gastric cancer, a comprehensive consideration is needed in treatment of gastric cancer.

Author Correction: NanoBRET binding assay for histamine H2 receptor ligands using live recombinant HEK293T cells

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: NanoBRET binding assay for histamine H2 receptor ligands using live recombinant HEK293T cells

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

VIRTUAL TARGET CONSTRUCTION FOR STRUCTURE-BASED SCREENING IN THE DISCOVERY OF HISTAMINE H2 RECEPTOR LIGANDS

Objective: This study aimed to develop validated targets to be employed in structure-based virtual screening (SBVS) to discover ligands for the human histamine H2 receptor (hHRH2). Methods: The virtual targets construction was initiated by homology modeling with the reference compound ranitidine as the ligand followed by 100 ns molecular dynamics (MD) simulations. During MD simulations, the snapshot with the lowest value of the free energy of binding was selected for further validation by re-docking simulations. All simulations were performed in YASARA-Structure. Results: The research presented here resulted in one validated target for the SBVS. Additionally, by employing a clustering module in MD simulations analysis in YASARA-Structure, more than ten different virtual targets are also available for further uses. Conclusion: The virtual targets resulted in this research offer possibilities to construct valid SBVS protocols to identify ligands for the hHRH2.