Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors

0574796 - ÚOCHB 2024 RIV GB eng J - Článek v odborném periodiku
Maltarollo, V. G. - da Silva, E. B. - Kronenberger, T. - Andrade, M. M. S. - de Lima Marques, G. V. - Oliveira, N. J. C. - Santos, L. H. - de Oliveira Rezende Júnior, C. - Martinho, A. C. C. - Skinner, D. - Fajtová, Pavla - Fernandes, T. H. M. - da Silveira dos Santos, E. - Gazolla, P. A. R. - de Souza, A. P. M. - da Silva, M. L. - dos Santos, F. S. - Lavorato, S. N. - Bretas, A. C. O. - Carvalho, D. T. - Franco, L. L. - Luedtke, S. - Giardini, M. A. - Poso, A. - Dias, L. C. - Podust, L. M. - Alves, R. J. - McKerrow, J. - Andrade, S. F. - Teixeira, R. R. - Siqueira-Neto, J. L. - O'Donoghue, A. - de Oliveira, R. B. - Ferreira, R. S.
Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors.
Future Medicinal Chemistry. Roč. 15, č. 11 (2023), s. 959-985. ISSN 1756-8919. E-ISSN 1756-8927
Institucionální podpora: RVO:61388963
Klíčová slova: computer-aided drug design * coronavirus * molecular docking * molecular dynamics simulations * Mpro * protease inhibitors * SARS-CoV-2 * virtual screening
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.2, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.4155/fmc-2023-0034

Aim: Discovery of novel SARS-CoV-2 main protease (Mpro) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover Mpro inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 Mpro with IC50 values of 0.4–3 μM. They were also shown to inhibit SARS-CoV-1 Mpro and human cathepsin L. Molecular dynamics simulations indicated the stability of the Mpro inhibitor complexes and the interaction of ligands at the subsites. Conclusion: This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 Mpro inhibitors.
Trvalý link: https://hdl.handle.net/11104/0344832