4.5. Famotidine (Pepcid)
Famotidine is a synthetic guandino-thiazole derivative (Figure 7) that acts as a potent and competitive H2-blocker. It was first approved by the U.S. FDA in 1986 and now is used as over-the-counter drug. It can be used orally or parenterally to treat gastroesophageal reflux disease, heartburn, and peptic ulcer [166]. Recently, a retrospective non-randomized study by Columbia University, Northwell Health, and Massachusetts General Hospital showed that famotidine, and not proton pump inhibitors, reduced the risk of intubation or death in hospitalized COVID-19 patients (n = 84) [167]. Furthermore, a case series indicated that COVID-19 patients (n = 10) who frequently self-administered a high-dose of oral famotidine (most frequent dose was 80 mg three times/day for a median of 11 days) reported significant symptoms improvement within 24 hours of starting famotidine [168]. Therefore, intravenously administered famotidine with standard of care (orally administered hydroxychloroquine and has progressed to include remdesivir) is currently being studied in a multi-site, randomized, double-blind, multi-arm historical control, comparative trial that is sponsored by Northwell Health, New York (NCT04370262; n = 942). Famotidine has been identified via virtual screening and molecular modeling, docking, and scoring as a potential inhibitor of Mpro [169], yet this potential is to be experimentally confirmed.