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?:abstract
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In this virtual drug repurposing study, we used 7922 FDA approved drugs and compounds in clinical investigation from NPC database Both apo and holo forms of SARS-CoV-2 Main Protease as well as Spike Protein/ACE2 were used for virtual screening Initially, docking was performed for these compounds at target binding sites The compounds were then sorted according to their docking scores which represent binding energies The first 100 compounds from each docking simulations were initially subjected to short (10 ns) MD simulations (in total 300 ligand-bound complexes), and average binding energies during MD simulations were calculated using the MM/GBSA method Then, the selected promising hit compounds based on average MM/GBSA scores were used in long (100-ns and 500-ns) MD simulations In total around 15 µs MD simulations were performed in this study Both docking and MD simulations binding free energy calculations showed that holo form of the target protein is more appropriate choice for virtual drug screening studies These numerical calculations have shown that the following 8 compounds can be considered as SARS-CoV-2 Main Protease inhibitors: Pimelautide, Rotigaptide, Telinavir, Ritonavir, Pinokalant, Terlakiren, Cefotiam and Cefpiramide In addition, following 5 compounds were identified as potential SARS-CoV-2 ACE-2/Spike protein domain inhibitors: Denopamine, Bometolol, Naminterol, Rotigaptide and Benzquercin These compounds can be clinically tested and if the simulation results validated, they may be considered to be used as treatment for COVID-19
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