Published Oct 4, 2019


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Ammara Akhtar

Waqar Hussain

Nouman Rasool



The HIV-1 protease plays an essential role in the replication cycle of HIV-1; therefore there is a direct need to develop novel inhibitors of the HIV-1 protease, which can cease the viral replication. The present study targets the discovery of potential inhibitors of HIV-1 protease from a set of phytochemicals. From 2505 phytochemicals, 108 compounds were docked, after screening, with the HIV-1 protease to analyze their inhibitory potential against the protease. DFT analysis was also conducted to study the reactivity of strongly docked compounds. Out of 108 phytochemicals, 38 compounds showed binding affinity greater than the desired threshold. Reactivity of these 38 inhibitors was also high as compared to other compounds, based on the DFT results. These results suggest that the selected 38 phytochemicals are drug candidates and they have the potential to be effectively used against HIV in the future.


HIV-1, Phytochemicals, Protease, Molecular docking, DFT, ADMET

[1] Siuki HA, Peyman N, Vahedian-Shahroodi M, Gholian-Aval M, Tehrani H. Health education intervention on HIV/AIDS prevention behaviors among health volunteers in healthcare centers: An applying the theory of planned behavior, Journal of Social Service Research, 1-7, 2018.
doi: 10.1080/01488376.2018.1481177

[2] Sobieski M, Przystupski D, Korzeniewska A, Kwiatkowski S, Górska A, Kotowski K, Baczyńska D. A review of current literature on the diagnosis, prophylaxis and treatment of HIV/ AIDS, World Scientific News, 110: 129-146, 2018.
http://www.worldscientificnew .com/wp-content/uploads/2018/08/WSN-110-2018-129-146-1.pdf

[3] Lawn SD, Butera ST, Folks TM.. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection, Clinical microbiology reviews, 14: 753-777, 2001.
doi: 10.1128/CMR.14.4.753-777.2001

[4] Fauci AS, Lane HC. Harrison's Internal Medicine, AccessMedicine, McGraw-Hill Education, New York, USA 2008.

[5] Joint United Nations Programme on HIV/AIDS, UNAIDS Data, 2017.

[6] Wlodawer A, Erickson JW. Structure-based inhibitors of HIV-1 protease, Annual review of biochemistry, 62: 543-585,1993.
doi: 10.1146/

[7] McQuade T, Tomasselli A, Liu L, Karacostas V, Moss B, Sawyer T, Heinrikson R, Tarpley W. A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation, Science, 247: 454-456, 1990.
doi: 10.1126/science.2405486

[8] Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D, Richman DD, Valentine FT, Jonas L, Meibohm A. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy, New England Journal of Medicine, 337: 734-739, 1997.
doi: 10.1056/NEJM199709113371102

[9] Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD. Decay characteristics of HIV-1-infected compartments during combination therapy, Nature, 387: 188, 1997.
doi: 10.1038/387188a0

[10] Clavel F, Hance AJ. HIV drug resistance, New England Journal of Medicine, 350: 1023-1035, 2004.
doi: 10.1056/NEJMra025195

[11] Veljkovic V, Mouscadet J-F, Veljkovic N, Glisic S, Debyser Z. Simple criterion for selection of flavonoid compounds with anti-HIV activity, Bioorganic & medicinal chemistry letters, 17: 1226-1232, 2007.
doi: 10.1016/j.bmcl.2006.12.029

[12] Friedman SH, DeCamp DL, Sijbesma RP, Srdanov G, Wudl F, Kenyon GL. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification, Journal of the American Chemical Society, 115: 6506-6509, 1993.
doi: 10.1021/ja00068a005

[13] Condra JH, Schleif WA, Blahy OM, Gabryelski LJ, Graham DJ, Quintero J, Rhodes A, Robbins HL, Roth E, Shivaprakash M. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors, Nature, 374: 569-571, 1995.
doi: 10.1038/374569a0

[14] Lindegaard B, Keller P, Bruunsgaard H, Gerstoft J, Pedersen B. Low plasma level of adiponectin is associated with stavudine treatment and lipodystrophy in HIV-infected patients, Clinical & Experimental Immunology, 135: 273-279, 2004.
doi: 10.1111/j.1365-2249.2004.02367.x

[15] Wiltink E. Antiviral drugs: present status and future prospects, The International journal of biochemistry, 26: 621-630, 1994.
doi: 10.1016/0020-711X(94)90161-9

[16] Tewtrakul S, Subhadhirasakul S, Puripattanavong J, and Panphadung T. HIV-1 protease inhibitory substances from the rhizomes of Boesenbergia pandurata Holtt, Songklanakarin Journal Science Technology, 25(4):503-508, 2003.

[17] Wadood A, Ghufran M, Jamal SB, Naeem M, Khan A, Ghaffar R. Phytochemical analysis of medicinal plants occurring in local area of Mardan, Biochemistry & Analytical Biochemistry, 2: 1-4, 2013.
doi: 10.4172/2161-1009.1000144

[18] Hussain W, Qaddir I, Mahmood S, Rasool N. In silico targeting of non-structural 4B protein from dengue virus 4 with spiropyrazolopyridone: study of molecular dynamics simulation, ADMET and virtual screening, VirusDisease, 29(2):147-156, 2018.
doi: 10.1007/s13337-018-0446-4

[19] Rasool N, Ashraf A, Waseem M, Hussain W, Mahmood S. Computational exploration of antiviral activity of phytochemicals against NS2B/NS3 proteases from dengue virus, Turkish Journal of Biochemistry, 44: 1-17, 2018.
doi: 10.1515/tjb-2018-0002

[20] Delgado-Jaime MU, DeBeer S. Expedited analysis of DFT outputs: Introducing moanalyzer, Journal of computational chemistry, 33(27): 2180-2185, 2012.
doi: 10.1002/jcc.23028

[21] Tayade NT, Shende AT, Tirpude MP. DFT study of L-alanine’s crystal, molecule and three linear molecules for optoelectronic behavior, International Journal of Scientific Research in Physics and Applied Sciences, 6(4): 23-27, 2018.
doi: 10.26438/ijsrpas/v6i4.2327

[22] Qaddir I, Rasool N, Hussain W, Mahmood S. Computer-aided analysis of phytochemicals as potential dengue virus inhibitors based on molecular docking, ADMET and DFT studies, Journal of vector borne diseases, 54(3): 255-262, 2017.
doi: 10.4103/0972-9062.217617

[23] Ramalingam M, Karthikeyan S, Kumar D. Docking Studies of HIV-1 Protease with Phytochemicals from Mappia Foetida, International Journal of Computer Applications, 43(4): 16-22, 2012.
doi: 10.5120/6091-8272

[24] Senthilvel P, Lavanya P, Kumar KM, Swetha R, Anitha P, Bag S, Sarveswari S, Vijayakumar V, Ramaiah S, Anbarasu A. Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly, Bioinformation, 9(18): 889-895, 2013.
doi: 10.6026/97320630009889

[25] Ibrahim AK, Radwan MM, Ahmed SA, Slade D, Ross SA, ElSohly MA, Khan IA. Microbial metabolism of cannflavin A and B isolated from Cannabis sativa, Phytochemistry, 71: 1014-1019, 2010.
doi: 10.1016/j.phytochem.2010.02.011

[26] Barros IBd, Daniel JFdS, Pinto JP, Rezende MI, Braz Filho R, Ferreira DT. Phytochemical and antifungal activity of anthraquinones and root and leaf extracts of Coccoloba mollis on phytopathogens, Brazilian Archives of Biology and Technology, 54(3): 535-541,2011.
doi: 10.1590/S1516-89132011000300015

[27] Sagbo IJ. Phytochemical analysis and antibacterial properties of aqueous and ethanol extracts of brachylaena elliptica (thurb.) dc. and brachylaena ilicifolia (lam.) phill. & schweick, Master of Science:
Biochemistry Dissertation, University of Fort Hare, 2015.

[28] Murphy BT, Cao S, Norris A, Miller JS, Ratovoson F, Andriantsiferana R, Rasamison VE, Kingston DG. Cytotoxic flavanones of Schizolaena hystrix from the Madagascar rainforest, Journal of natural products, 68(3): 417-419, 2005.
doi: 10.1021/np049639x

[29] Rao C, Verma A, Gupta P, Vijayakumar M. Anti-inflammatory and anti-nociceptive activities of Fumaria indica whole plant extract in experimental animals, Acta Pharmaceutica, 57(4): 491-498, 2007.
doi: 10.2478/v10007-007-0039-z

[30] Pezzuto JM, Beecher C, Fong H, Farnsworth NR, Mehta RG, Moon RC, Hedayat S, Udeani GO, Moriarty R, Kinghom A. Discovery and characterization of natural product cancer chemopreventive agents, Atta-ur-Rahman and M. Iqbal (eds.), New
Trends in Natural Product Chemistry, Harwood Academic Publishers:
Chur, Switzerland: 95-107,1998.

[31] Wu X, Liao H, Wu K, Cui L. Chemical constituents from the seeds of Amorpha fruticosa and their chemotaxonomic significance, Open Access Library Journal, 3: 1-7, 2016.
doi: 10.4236/oalib.1102740

[32] Lagunin AA, Goel RK, Gawande DY, Pahwa P, Gloriozova TA, Dmitriev AV, Druzhilovsky DS. Chemo-and bioinformatics resources for in silico drug discovery from medicinal plants beyond their traditional use: a critical review, Natural product reports, 31: 1585-161, 2014.
doi: 10.1039/c4np00068d

[33] Wishart DS. Online Databases and Web Servers for Drug Metabolism Research. Edited by Johannes Kirchmair, Wiley Publishers, New Jersey, US, 2014.

[34] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Advanced drug delivery reviews, 46(1-3): 3-26, 2001.
doi: 10.1016/S0169-409X(00)00129-0

[35] Duchowicz PR, Talevi A, Bellera C, Bruno-Blanch LE, Castro EA. Application of descriptors based on Lipinski’s rules in the QSPR study of aqueous solubilities, Bioorganic & medicinal chemistry, 15(11): 3711-3719, 2007.
doi: 10.1016/j.bmc.2007.03.044

[36] Kavitha R, Karunagaran S, Chandrabose SS, Lee KW, Meganathan C. Pharmacophore modeling, virtual screening, molecular docking studies and density functional theory approaches to identify novel ketohexokinase (KHK) inhibitors, Biosystems, 138: 39-52, 2015.
doi: 10.1016/j.biosystems.2015.10.005

[37] Sakkiah S, Lee KW. Pharmacophore-based virtual screening and density functional theory approach to identifying novel butyrylcholinesterase inhibitors, Acta Pharmacologica Sinica, 33: 964-978, 2012.
doi: 10.1038/aps.2012.21

[38] Sathyanarayanmoorthi V, Karunathan R, Kannappan V. Molecular modeling and spectroscopic studies of Benzothiazole, Journal of Chemistry, 2013: 14, 2013.
doi: 10.1155/2013/258519

[39] Queiroz AN, Gomes BA, Moraes Jr WM, Borges RS. A theoretical antioxidant pharmacophore for resveratrol, European journal of medicinal chemistry, 44(4): 1644-1649, 2009.
doi: 10.1016/j.ejmech.2008.09.023
How to Cite
Akhtar, A., Hussain, W., & Rasool, N. (2019). Probing the Pharmacological Binding Properties, and Reactivity of Selective Phytochemicals as Potential HIV-1 protease Inhibitors. Universitas Scientiarum, 24(3), 441–464.
Bioinformatics and modeling