In silico evaluation of the inhibitory effect of antiretrovirals Atazanavir and Darunavir on the main protease of SARS-CoV-2: docking studies and molecular dynamics
DOI:
https://doi.org/10.33448/rsd-v9i8.6562Keywords:
Molecular anchorage; Protease inhibitor; Use of medicines.Abstract
SARS-CoV-2 is part of an RNA virus family described again in 2019, causing the Covid-19 disease. The integration of computational strategies is of great importance in the identification and development of promising new compounds. Atazanavir and Darunavir, were designed to combat resistance to mutant drugs mainly by increasing the number of polar interactions with the main atoms in the HIV protease chain. This study aims to assess the molecular interaction of the drugs Atazanavir and Darunavir with the main SARS-CoV-2 protease through docking and molecular dynamics studies. This is a descriptive, experimental study with a qualitative and quantitative approach on the subject. For that, using the programs BIOVIA Discovery Studio, PyMol, AutoDock Tools 1.5.6, AutoDock Vina, the modeling and simulation of the anchoring of the drug at the action site were carried out. Lower scores were demonstrated, with -7.0 (Darunavir) the closest to the UAW 247 Inhibitor. It is possible to notice that the drugs showed similar residual bonds, also, in relation to the protease structure, the closest tested molecule was Atazanavir. Taking into account the stability of the RMSD values, it is valid to infer that in relation to the UAW 247 inhibitor, the drug Atazanavir is the one that best resembles, unlike Darunavir, which presents greater variations. The two drugs fit into the binding site mainly due to electrostatic interactions and hydrogen bonds. Atazanavir is the most similar to molecular activity, and Darunavir is the one with the best anchoring score.
References
Baildya, N., Ghosh, N. N., & Chattopadhyay, A. P. (2020). Inhibitory activity of hydroxychloroquine on COVID-19 main protease: An insight from MD-simulation studies. Journal of Molecular Structure, 128595. doi:10.1016/j.molstruc.2020.128595
Boopathi, S., Poma, A. B., & Kolandaivel, P. (2020). Novel 2019 Coronavirus Structure, Mechanism of Action, Antiviral drug promises and rule out against its treatment. Journal of Biomolecular Structure and Dynamics, 1–14. doi:10.1080/07391102.2020.1758788
Bursulaya, B. D., Totrov, M., Abagyan, R., & Brooks III, C. L. (2003). Comparative study of several algorithms for flexible ligand docking. Journal of Computer-Aided Molecular Design, 17(11), 755–63. doi:10.1023/b:jcam.0000017496.76572.6f
Ferreira, L., Santos, R., Oliva, G., & Andricopulo, A. (2015). Molecular Docking and Structure-Based Drug Design Strategies. Molecules, 20(7), 13384–421. doi:10.3390/molecules200713384
Lai, C. C., Shih, T. P., Ko, W. C., Tang, H. J., & Hsueh, P. R. (2020). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges. International Journal of Antimicrobial Agents, 55(3), 105924. doi:10.1016/j.ijantimicag.2020.105924
Lima, C. M. A. O. (2020). Informações sobre o novo coronavírus (COVID-19). Radiol Bras, 53(2), 5-7, 2020. doi:10.1590/0100-3984.2020.53.2e1
Menéndez-Arias, L., & Tözsér, J. (2008). HIV-1 protease inhibitors: effects on HIV-2 replication and resistance. Trends in Pharmacological Sciences, 29(1), 42–49. doi:10.1016/j.tips.2007.10.013
Mittal, L., Kumari, A., Srivastava, M., Singh, M., & Asthana, S. (2020). Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach. Journal of Biomolecular Structure and Dynamics, 1–26. doi:10.1080/07391102.2020.1768151
Pereira, A. S., et al. (2018). Methodology of cientific research. [e-Book]. Santa Maria City. UAB / NTE/UFSM Editors. Retrieved from: https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1
Sousa G. A., Martins I. V. O., Pimentel V. D., & Sousa J. A. (2020). Análise in silico da farmacodinâmica, farmacocinética e toxicidade de dois compostos isolados da Actinidia deliciosa para investigação do seu potencial anti-hiperlipêmico. Research, Society and Development, 9(7), 1-20, e790974679. doi:10.33448/rsd-v9i7.4679
Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 32, 455-61. doi:10.1002/jcc.21334
Uciechowska-Kaczmarzyk, U., Chauvot de Beauchene, I., & Samsonov, S. A. (2019). Docking software performance in protein-glycosaminoglycan systems. Journal of Molecular Graphics and Modelling, 90, 42–50. doi:10.1016/j.jmgm.2019.04.001
Wang, Q., He, J., Wu, D., Wang, J., Yan, J., & Li, H. (2015). Interaction of α-cyperone with human serum albumin: Determination of the binding site by using Discovery Studio and via spectroscopic methods. Journal of Luminescence, 164, 81–5. doi:10.1016/j.jlumin.2015.03.025
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2020 José Danilo de Sousa Silva, Samuel da Costa Leite, Maria Thalita Sobral da Silva
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
