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Molecular Docking Studies of HIV-1 Protease-, Integrase- and Reverse-Transcriptase with Delta-9-tetrahydrocannabinol and Curcumin as Two Herbal Ligands

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Abstract

HIV-1 is a human immunodeficiency virus, which has three enzymes, Integrase (IN), Protease (PR) and Reverse-transcriptase (RT). Inhibitor pattern of two herbal ligands include Curcumin (CRC) and Delta-9-tetrahydrocannabinol (THC) with HIV-1 enzymes were investigated by using molecular docking. These ligands are chosen base on the Lipinski’s rules as an herbal inhibitor of HIV-1 virus. We found that CRC and THC ligands have similar orientation in active sites of IN, PR, and RT enzymes. The highest binding energy between PR, IN and RT with CRC and THC ligands are –8.8 and –8.7 Kcal/mol, respectively that reported for PR enzyme. Residues Asp25, Asp29, Asp30 placed in very important catalytic region in both chains of protease enzyme including the central domain which have H-bond with curcumin and THC. Moreover, residue Ile50 is the most flexible region of protease enzyme which plays a significant role in catalytic activity that has interaction with CRC and THC.

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References

  1. Gupta, S.P., Shaik, B., Ahmad, I., and Agrawal, V.K., In silico Studies on HIV-1 Integrase Inhibitors: A, 2016.

  2. Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A., et al., Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor, Science, 1992, vol. 256, no. 5065, pp. 1783–1790.

  3. Weissbrich, B., Heinkelein, M., and Jassoy, C., Evaluation of drug resistance in HIV infection, 2002.

  4. Luo, M., Capina, R., Daniuk, C., Tuff, J., et al., Immunogenicity of sequences around HIV-1 protease cleavage sites: potential targets and population coverage analysis for a HIV vaccine targeting protease cleavage sites, Vaccine, 2013, vol. 31, no. 29, pp. 3000–3008.

  5. Jiang, R., Zhang, X., and Zhang, M.Q., Basics of Bioinformatics, Springer, 2016.

  6. Luscombe, N.M., Greenbaum, D., and Gerstein, M., What is bioinformatics? An introduction and overview, Yearb. Med. Inform., 2001, vol. 10, no. 01, pp. 83–100.

  7. Mukesh, B. and Rakesh, K., Review on Molecular docking, Ijrap., 2011, vol. 2, no. 6, pp. 1746–51.

  8. Grinter, S.Z. and Zou, X., Challenges, applications, and recent advances of protein-ligand docking in structure-based drug design, Molecules, 2014, vol. 19, no. 7, pp. 10150–10176.

  9. Berdyshev, E.V., Cannabinoid receptors and the regulation of immune response, Chem. Phys. Lipids., 2000, vol. 108, no. 1–2, pp. 169–190.

  10. Voth, E.A. and Schwartz, R.H., Medicinal plications of delta-9-tetrahydrocannabinol and marijuana, Ann. Intern. Med., 1997, vol. 126, no. 10, pp. 791–798.

  11. Beal, J.E., Olson, R., Laubenstein, L., Morales, J.O., et al., Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS, J. Pain Symptom Manage, 1995, vol. 10, no. 2, pp. 89–97.

  12. Hurd, Y.L., Wang, X., Anderson, V., Beck, O., et al., Marijuana impairs growth in mid-gestation fetuses, Neurotoxicol. Teratol., 2005, vol. 27, no. 2, pp. 221–229.

  13. Nahas, G.G., Suciu-Foca, N., Armand, J.-P., and Morishima, A., Inhibition of cellular mediated immunity in marihuana smokers, Science, 1974, vol. 183, no. 4123, pp. 419–420.

  14. Lee, M., Yang, K.H., and Kaminski, N.E., Effects of putative cannabinoid receptor ligands, anandamide and 2-arachidonyl-glycerol, on immune function in B6C3F1 mouse splenocytes, J. Pharmacol. Exp. Ther., 1995, vol. 275, no. 2, pp. 529–536.

  15. Bouaboula, M., Rinaldi, M., Carayon, P., Carillon, C., et al., Cannabinoid-receptor expression in human leukocytes, Eur. J. Biochem., 1993, vol. 214, no. 1, pp. 173–180.

  16. Fanali, G., Cao, Y., Ascenzi, P., Trezza, V., et al., Binding of δ9-tetrahydrocannabinol and diazepam to human serum albumin, IUBMB Life, 2011, vol. 63, no. 6, pp. 446–451.

  17. Huestis, M.A., Pharmacokinetics and metabolism of the plant cannabinoids, Δ9-tetrahydrocannibinol, cannabidiol and cannabinol, in Cannabinoids, Springer, 2005, pp. 657–690.

  18. Chen, W., Crawford, R.B., Kaplan, B.L., and Kaminski, N.E., Modulation of HIV GP120 Antigen-Specific Immune Responses In Vivo by Δ-9-Tetrahydrocannabinol, J. Neuroimmune Pharmacol., 2015, vol. 10, no. 2, pp. 344–355.

  19. Ammon, H.P.T., Anazodo, M.I., Safayhi, H., Dhawan, B.N., et al., Curcumin: a potent inhibitor of leukotriene B4 formation in rat peritoneal polymorphonuclear neutrophils (PMNL), Planta Med., 1992, vol. 58, no. 2, pp. 226–226.

  20. Araujo, C.A.C. and Leon, L.L., Biological activities of Curcuma longa L., Mem. Inst. Oswaldo Cruz., 2001, vol. 96, no. 5, pp. 723–728.

  21. Ammon, H.P. and Wahl, M.A., Pharmacology of Curcuma longa, Planta Med., 1991, vol. 57, no. 01, pp. 1–7.

  22. Vajragupta, O., Boonchoong, P., Morris, G.M., and Olson, A.J., Active site binding modes of curcumin in HIV-1 protease and integrase, Bioorg. Med. Chem. Lett., 2005, vol. 15, no. 14, pp. 3364–3368.

  23. Goldgur, Y., Craigie, R., Cohen, G.H., Fujiwara, T., et al., Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design, Proc. Natl. Acad. Sci., 1999, vol. 96, no. 23, pp. 13040–13043.

  24. Chen, Z., Li, Y., Chen, E., Hall, D.L., et al., Crystal structure at 1.9-A resolution of human immunodeficiency virus (HIV) II protease complexed with L-735,524, an orally bioavailable inhibitor of the HIV proteases, J. Biol. Chem., 1994, vol. 269, no. 42, pp. 26344–26348.

  25. Karlsson, A.C., Deeks, S.G., Barbour, J.D., Heiken, B.D., et al., Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene, J. Virol., 2003, vol. 77, no. 12, pp. 6743–6752.

  26. Rose, R.B., Craik, C.S., Douglas, N.L., and Stroud, R.M., Three-dimensional structures of HIV-1 and SIV protease product complexes, Biochemistry, 1996, vol. 35, no. 39, pp. 12933–12944.

  27. Trott, O. and Olson, A.J., AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput.Chem., 2010, vol. 31, no. 2, pp. 455–461.

  28. Autodock, A.J., Morris, G.M., Goodsell, D.S., Halliday, R.S., et al., Automated Docking Using a Lamarckian Genetic Algorithm and an Empirical Binding Free Energy Function, 1998.

  29. Hetényi, C. and Van Der Spoel, D., Efficient docking of peptides to proteins without prior knowledge of the binding site, Protein Sci., 2002, vol. 11, no. 7, pp. 1729–1737.

  30. Yunta, M.J., Docking and ligand binding affinity: uses and pitfalls, Am. J. Model. Optim., 2016, vol. 4, pp. 74–114.

  31. Masoud, M. and Taylor-Robinson, A., Prediction of epitopes of viral antigens recognized by cytotoxic T Lymphocytes as an immunoinformatics approach to anti-HIV/AIDS vaccine design, 2015.

  32. Kulkosky, J., Jones, K.S., Katz, R.A., Mack, J.P., et al., Residues critical for retroviral integrative recombination in a region that is highly conserved among retroviral/retrotransposon integrases and bacterial insertion sequence transposases, Mol. Cell. Biol., 1992, vol. 12, no. 5, pp. 2331–2338.

  33. Baker, T.A. and Luo, L., Identification of residues in the Mu transposase essential for catalysis, Proc. Natl. Acad. Sci., 1994, vol. 91, no. 14, pp. 6654–6658.

  34. Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., et al., UCSF Chimera—a visualization system for exploratory research and analysis, J. Comput. Chem., 2004, vol. 25, no. 13, pp. 1605–1612.

  35. Aggarwal, B.B., Bhatt, I.D., Ichikawa, H., Ahn, K.S., et al., 10 Curcumin—Biological and Medicinal Properties, 2006.

  36. Donnelly, J. and Hernández, F.E., Conformational Study of Cannabinoid Docking to Cannabinoid Receptor 1 (CB1) via Linear and Nonlinear Circular Dichroism, J. Phys. Chem. Biophys., 2016, vol. 6, no. 227, pp. 2161–0398.

  37. Choy, Y.B. and Prausnitz, M.R., The rule of five for non-oral routes of drug delivery: ophthalmic, inhalation and transdermal, Pharm. Res., 2011, vol. 28, no. 5, pp. 943–948.

  38. Pari, L., Tewas, D., and Eckel, J., Role of curcumin in health and disease, Arch. Physiol. Biochem., 2008, vol. 114, no. 2, pp. 127–149.

  39. Martin-Santos, R., a Crippa, J., Batalla, A., Bhattacharyya, S., et al., Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers, Curr. Pharm. Des., 2012, vol. 18, no. 32, pp. 4966–4979.

  40. Cosconati, S., Marinelli, L., Lavecchia, A., and Novellino, E., Characterizing the 1, 4-dihydropyridines binding interactions in the L-type Ca2+ channel: model construction and docking calculations, J. Med. Chem., 2007, vol. 50, no. 7, pp. 1504–1513.

  41. Huey, R. and Morris, G.M., Using AutoDock 4 with AutoDocktools: a tutorial, Scripps Res. Inst. USA, 2008, pp. 54–56.

  42. Davood, A., reza Nematollahi, A., Iman, M., and Shafiee, A., Synthesis and docking studies of new 1, 4-dihydropyridines containing 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent as novel calcium channel agonist, Arch. Pharm. Res., 2009, vol. 32, no. 4, pp. 481–487.

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Authors and Affiliations

  1. Department of Chemistry, Payame Noor University, Tehran 19395-4697, Iran

    S. Esmaeili & F. Ravari

  2. Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran

    H. Mosaddeghi

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Esmaeili, S., Mosaddeghi, H. & Ravari, F. Molecular Docking Studies of HIV-1 Protease-, Integrase- and Reverse-Transcriptase with Delta-9-tetrahydrocannabinol and Curcumin as Two Herbal Ligands. J Evol Biochem Phys 57, 281–288 (2021). https://doi.org/10.1134/S0022093021020101

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