The COVID-19 pandemic has driven great interest in the therapeutic potential of repurposed drugs with well-established benefits and safety profiles (toxicity, bioavailability, etc.), many of which act via signal transduction pathways. One category of such drugs is those that reduce acid production in gastroenterological contexts. Acid-suppressing drugs belong to two main classes, based on their mechanisms of action: (i) proton-pump inhibitors (PPIs) sterically block H+/K+-ATPase pumps, impeding the final step of acid release in the gastric mucosa. (ii) Histamine H2 receptor antagonists (H2RA) competitively bind the H2R, a type of G-protein coupled receptor (GPCR),1 and block the natural stimulation of...