Abstract
This paper presents a systematic analysis of the possibility of repurposing commercial drugs through Molecular Docking and Quantitative Structure and Activity Relationship (QSAR) explorations for the treatment of patients infected with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To do this, we checked the chances of inhibiting the main protease (Mpro) of SARS-CoV-2, the cyclo-oxygenase-2 (COX-2) enzyme, and the spike viral protein by commercial drugs. The molecular structures of the ligands were obtained from the DrugBank database. All ligand molecular structures were previously optimised using the Gaussian 09 package through the GFN-xTB model. The Marvin Sketch program verified the lipophilic character (pH = 7.4) and the manifestation form. The entire molecular docking study was developed using the AutoDock Vina 1.1.2 software. DFT calculations compared the nature of intermolecular forces involving different drugs on the same protein, considering the common residues in these interactions with other drugs. Non-covalent interactions (NCI) analysis shows weak interactions involving 6LU7-Celecoxib, 6LU7-Remdesivir, Celecoxib-3NT1 and Naproxen-3NT1 complexes. It was found that affinities involving the Mpro-drug, COX-2-drug and S-drug complexes indicate a better cost-benefit relationship for the drug celecoxib. However, celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) and can increase the risk of myocardial infarction. Thus, the prophylactic use of these drugs should only be done by infected patients under medical supervision, as is already done with dexamethasone. The anti-inflammatory celecoxib presented the best cost-benefit: the second-best inhibitor of the Mpro protein, the best inhibitor of the COX-2 protein (alongside naproxen), and the third-best inhibitor of the protein S. We suggest that the list of medications presented here be considered for future clinical trials.
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Acknowledgements
G. F. M. and T. S. C. are grateful to the CAPES for the PhD scholarship. D. A. C. F. is thankful to the PET/IQ-UnB/SESu/MEC for the tutor fellowship.
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The authors thank the financial support provided by COPEI/DPG/UnB in 2020 for developing this research.
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G.F.M. conceived the study performed and carried out the interpretation of the theoretical data. T.S.C. assisted in the understanding of the theoretical data. D.A.C.F. conceived the analysis performed and carried out the interpretation of the theoretical data.
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Martins, G.F., Castro, T.S. & Ferreira, D.A.C. Drug repurposing for the treatment of patients infected with SARS-CoV-2. Netw Model Anal Health Inform Bioinforma 13, 15 (2024). https://doi.org/10.1007/s13721-024-00453-6
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DOI: https://doi.org/10.1007/s13721-024-00453-6