Abstract

Background: An ongoing global public health concern is the emerging COVID-19 pandemic triggered by acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mpro, a main protease of SARSCoV- 2, has been established as a potential drug target because of its direct role in viral replication and ability to infiltrate the multiple host pathways.

Objective: This research aims to classify new therapeutic drug candidates who may be repositioned for COVID-19 therapeutics.

Methods: We have taken similar drug compounds of Dexamethasone and targeted the main protease of SARS-CoV-2 (Mpro) along with the key molecules involved in the 'cytokine storm.' Further, we did MD simulations and calculated the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) on the active site of the main protease of SARS-CoV-2 (Mpro) and TNF-α, IL-6, & IL-1β to explore the binding affinity and stability.

Results: Based on our study outcome, Triamcinolone emerged as the most promising inhibitor of the main protease of SARS-CoV-2 (Mpro) and the cytokine storm molecules, i.e., TNF-α, IL-6, and IL-1β.

Conclusion: This research investigates the repositioning of COVID-19 drugs as a new therapeutic application.

Keywords: COVID-19, cytokine storm, main protease, molecular docking, MD simulation, protease inhibitor, triamcinolone.