Drug repurposing: Dipeptidyl peptidase IV (DPP4) inhibitors as potential agents to treat SARS-CoV-2 (2019-nCov) infection

The current outbreak of severe acute respiratory distress syndrome (SARS) or nCOVID-19 pandemic, caused by the coronavirus-2 (CoV-2), continues to wreak havoc globally. Unfortunately, there are no concrete treatment options available which has severely hampered the pharmacotherapy of this devastating infection. This calls for an urgent need to consider alternative strategies which can be employed quickly, as discovering new drugs for SARS-CoV-2 infections is a time consuming and expensive proposition. In this regard, drug repurposing is an appealing approach which can provide rapid access to therapeutics with proven record of safety and efficacy. Accordingly, we investigated the drug repurposing potential of a library of dipeptidyl peptidase 4 (DPP4) inhibitors which are currently marketed for type-2 diabetes, to treat SARS-CoV-2 infections. Computational studies were conducted in the crystal structure of the substrate binding site of viral protease, the SARS-CoV-2 M^pro dimer, which led to the identification of three marketed DPP4 inhibitors; gemigliptin, linagliptin and evogliptin exhibiting favorable binding, in the SARS-CoV-2 M^pro dimer, viral protease. These studies supports further investigation of repurposing DPP4 class of inhibitors and their potential in treating SARS-CoV-2 infections, especially in elderly patients with type-2 diabetes, who are at a greater risk of suffering from increased disease severity and mortality.