Proton pump inhibitors (PPIs) belong to a well-known class of pharmaceutical agents which target the gastric epithelial H+/K+ ATPase. Although the major therapeutic uses of the PPIs are in gastric-acid related diseases, evidences are suggestive of a pleiotropic nature of the compounds. They have been used for the treatment of conditions such as eosinophilic esophagitis and Helicobacter pylori infection, in addition to their conventional use in gastro-oesophageal reflux disease and peptic ulcers. The current pandemic of COVID-19 has put forward a challenge to find treatment options. While multiple studies have been conducted, and many are currently on-going, we have not been able to come up with any specific agent against SARS-CoV-2. PPIs have shown antiviral potencies in various in vivo and in vitro studies. Results from these studies point toward a promising role of PPIs for infections caused by Marburg virus, Influenza virus and Rhinovirus to mention a few. However, neither have they been considered for any clinical trials nor have any guidelines suggested their re-purposing against SARS-CoV-2 till date. In this review, we discuss the probable pathways and cellular machineries via which PPIs could show beneficial therapeutic effects against the novel coronavirus based on the existing evidences.