In Silico Analyzes for the Inhibition of HIV Protease by Ritonavir and Indinavir
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Abstract
Introduction: This research was conducted to investigate the molecular interaction of HIV protease inhibitor drugs using molecular docking. HIV protease is responsible for processing gag and gag-polyproteins during virion maturation. The activity of this enzyme is essential against viral infections and has beneficial therapeutic effects on HIV treatment.
Materials and Methods: To meet the aim of the study, indinavir and ritonavir were selected as HIV Protease inhibitor drugs. The necessary information on molecular docking was collected through information servers, such as Drug bank and Program database (PDB). Then, molecular docking was performed using Molegro virtual docker software. In order to check the stability of the resulting complex structure and its cellular penetration, a molecular dynamics simulation was run for 50 nanoseconds using GROMACS2019.6 package and Amber99SB force force field. During the molecular dynamics simulation, root mean square deviations (RMSD), root mean square fluctuations (RMSF), the radius of gyration (RG), hydrogen bonds, and distance between ligands and complex were investigated.
Results: The obtained results indicated that the RMSD of the complex of the ligands and HIV protease at the end of 50 nanoseconds had a linear slope. Hydrogen bonds decreased at beginning of simulation but they increase at the end of simulation However RG was decreased at the end of the simulation Also the RMSF was decreased at the end of simulation rather than beginning of simulation, So all the obtained results showing the stability and strength of the structure.
Conclusion: Molecular docking method can indicate the relationship between structure-activity and the effectiveness of ligands on HIV protease based on the level of interaction between the ligands and the receptors.
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References
Bitencourt-Ferreira G and de Azevedo WF Jr. Molegro virtual docker for docking. Methods Mol Biol. 2019; 2053: 149-167. DOI: https://doi.org/10.1007/978-1-4939-9752-7_10
Scheraga HA, Khalili M, and Liwo AJARPC. Protein-folding dynamics: Overview of molecular simulation techniques. Annu Rev Phys Chem. 2007; 58: 57-83. DOI: https://doi.org/10.1146/annurev.physchem.58.032806.104614
Kabsch W and Sander C. Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983; 22: 2577-2637. DOI: https://doi.org/10.1002/bip.360221211
He H. Vaccines and antiviral agents. In: Romanowski V, editor. Current Issues in Molecular Virology. Viral Genetics and Biotechnological Applications. Rijeka, Croatia: InTech; 2013. p. 239-250. Available at: https://b2n.ir/z17893
Bianchin MD, Prebianca G, Immich MF, Teixeira ML, Colombo M, Koester LS. Monoolein-based nanoparticles containing indinavir: A taste-masked drug delivery system. Drug Dev Ind Pharm. 2021; 47(1): 83-91. DOI: https://doi.org/10.1080/03639045.2020.1862167
Sadus RJ. Molecular simulation of fluids: Elsevier. Theory, algorithms, and object-orientation. 1st ed. Amesterdam, Netherland; Elsevier Science B.V; 2002. Available at: https://b2n.ir/d94769
Parks JM and Smith JC. How to discover antiviral drugs quickly. N Engl J Med. 2020; 382(23): 2261-2264. DOI: https://doi.org/10.1056/nejmcibr2007042
Shin WJ and Seong BL. Novel antiviral drug discovery strategies to tackle drug-resistant mutants of influenza virus strains. Expert Opin Drug Discov. 2019; 14(2):153-168. DOI: https://doi.org/10.1080/17460441.2019.1560261
Connolly SA, Jackson JO, Jardetzky TS, and Longnecker R. Fusing structure and function: A structural view of the herpesvirus entry machinery. Nat Rev Microbiol. 2011; 9(5): 369-381. DOI: https://doi.org/10.1038/nrmicro2548
Balfour JR HH. Resistance of herpes simplex to acyclovir. Ann Intern Med. 1983; 98(3): 404-406. DOI: https://doi.org/10.7326/0003-4819-98-3-404
Cvetkovic RS and Goa KL. Lopinavir/ritonavir: A review of its use in the management of HIV infection. Drugs. 2003; 63(8): 769-802. DOI: https://doi.org/10.2165/00003495-200363080-00004
Fyfe J, Keller P, Furman P, Miller Rl, and Elion Gb. Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl) guanine. J Biol Chem.
; 253(24): 8721-8727. Available at: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=PASCAL7950382766
Hoetelmans RM, Meenhorst PL, Mulder JW, Burger DM, Koks CH, and Beijnen JH. Clinical pharmacology of HIV protease inhibitors: Focus on saquinavir, indinavir, and ritonavir. Pharm World Sci. 1997; 19(4): 159-175. DOI: https://doi.org/10.1023/a:1008629608556
Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, Akram M, Riaz M, Rasool G, et al. A review: Mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol. 2021; 35: 1-12. DOI: https://doi.org/10.1177/20587384211002621
Cernik C, Gallina K, and Brodell RT. The treatment of herpes simplex infections: An evidence-based review. Arch Intern Med. 2008; 168(11): 1137-1144. DOI: https://doi.org/10.1001/archinte.168.11.1137
Moyle G and Gazzard B. Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs. 1996; 51(5): 701-712. DOI: https://doi.org/10.2165/00003495-199651050-00001
Gass RJ, Gal J, Fogle PW, Detmar-Hanna D, and Gerber JG. Neither dapsone hydroxylation nor cortisol 6beta-hydroxylation detects the inhibition of CYP3A4 by HIV-1 protease inhibitors. Eur J Clin Pharmacol. 1998; 54(9-10): 741-747. DOI: https://doi.org/10.1007/s002280050545
Mansouri S, Habibi Fazi L, and Minuchehr Z. Molecular dynamics simulations of Aβ (1-42) and Aβ (1-40): A comparative study to determine their role in the development of Alzheimer's disease. NCMBJ. 2016; 6(24): 43-50.
Saffari-Chaleshtori J, Jamali N, Heydari E, and Ghatreh Samani K. Molecular dynamics simulation study of the effect of hesperetin on pre-apoptotic factors of Bad, Bak, and Bim. SJKU. 2019; 23(6): 1-9.
Tazikeh-Lemeski E. The study of the interaction between amyloid beta protein and zinc ion and its role in Alzheimer's disease. Med Sci. 2015; 25(3): 198-205.
Asadi P, Alivaisi E, and Norollahi moghadam N. Pharmaceutical inhibitor design against cyclooxygenase2 to reduce the inflammation and pain. J Ilam Univ Med Sci. 2017; 24(6): 203-212.