Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L
Abstract
:1. Introduction
2. Results
2.1. Structural Characterization of Mpro in Apo and MG-132 Bound Forms
2.2. Mpro Inhibition Mechanism by MG-132
2.3. MG-132 and Cathepsin-L Inhibition
2.4. Docking of MG-132 in Cathepsin-L Binding Site
3. Discussion
4. Materials and Methods
4.1. Protein Expression and Purification
4.2. Mpro Enzymatic Activity
4.3. Cathepsin-L Inhibition Assay
4.4. Thermostability Assay
4.5. Crystallization
4.6. Data Collection, Data Reduction, Structure Determination, Refinement and Final Model Analysis
4.7. Molecular Docking
4.8. Sequence Alignment
4.9. Docking Validation
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Costanzi, E.; Kuzikov, M.; Esposito, F.; Albani, S.; Demitri, N.; Giabbai, B.; Camasta, M.; Tramontano, E.; Rossetti, G.; Zaliani, A.; et al. Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L. Int. J. Mol. Sci. 2021, 22, 11779. https://doi.org/10.3390/ijms222111779
Costanzi E, Kuzikov M, Esposito F, Albani S, Demitri N, Giabbai B, Camasta M, Tramontano E, Rossetti G, Zaliani A, et al. Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L. International Journal of Molecular Sciences. 2021; 22(21):11779. https://doi.org/10.3390/ijms222111779
Chicago/Turabian StyleCostanzi, Elisa, Maria Kuzikov, Francesca Esposito, Simone Albani, Nicola Demitri, Barbara Giabbai, Marianna Camasta, Enzo Tramontano, Giulia Rossetti, Andrea Zaliani, and et al. 2021. "Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L" International Journal of Molecular Sciences 22, no. 21: 11779. https://doi.org/10.3390/ijms222111779