5  Proton pump inhibitors
To alleviate the side-effects of NSAIDs, proton pump inhibitors (PPIs) are often given concomitantly. It is important to note that PPIs can inhibit V-ATP-ase, the enzyme responsible for maintaining pH in endosomes. As a consequence, PPIs can induce cytosolic acidification and lysosomal and endosomal alkalinization [45,46]. As discussed above, this effect could be beneficial in patients with COVID-19. In the context of the direct and indirect antiviral effects of indomethacin discussed above, and its well-known gastrointestinal side-effects, a combination of indomethacin and PPIs should be investigated further as a potential therapeutic strategy in COVID-19. Additionally, ACE-2, which acts as a primary receptor for SARS-CoV-2 host cell entry, is a well-known intestinal transporter involved in amino acid absorption throughout the human small intestine [47], and gastrointestinal symptoms are reported to be part of the clinical presentation of COVID-19 [48,49]. Therefore, targeting the gastrointestinal system could have a dual benefit as lysosomotropic agents could provide symptomatic relief and reduce viral dissemination. The possibility that the faecal-oral transmission route is involved in viral spread, in combination with the recent finding that viral RNA remained positive in faeces even after negative conversion of viral RNA in the respiratory system, further supports the idea that lysosomotropic agents that primarily target the gastrointestinal system should be considered as part of the treatment of COVID-19 [48].