Pharmacophore-based approaches in the rational repurposing technique for FDA approved drugs targeting SARS-CoV-2 Mpro

Abstract

Novel coronavirus (CoV) is the primary etiological virus responsible for the pandemic that started in Wuhan in 2019–2020. This viral disease is extremely prevalent and has spread around the world. Preventive steps are restricted social contact and isolation of the sick individual to avoid person-to-person transmission. There is currently no cure available for the disease and the search for novel medications or successful therapeutics is intensive, time-consuming, and laborious. An effective approach in managing this pandemic is to develop therapeutically active drugs by repurposing or repositioning existing drugs or active molecules. In this work, we developed a feature-based pharmacophore model using reported compounds that inhibit SARS-CoV-2. This model was validated and used to screen the library of 565 FDA-approved drugs against the viral main protease (M^pro), resulting in 66 drugs interacting with M^pro with higher binding scores in docking experiments than drugs previously reported for the target diseases. The study identified drugs from many important classes, viz. D₂ receptor antagonist, HMG-CoA inhibitors, HIV reverse transcriptase and protease inhibitors, anticancer agents and folate inhibitors, which can potentially interact with and inhibit the SARS-CoV-2 M^pro. This validated approach may help in finding the urgently needed drugs for the SARS-CoV-2 pandemic with infinitesimal chances of failure.