A COMPUTATIONAL APPROACH ON UNDERSTANDING STRUCTURAL INTERACTIONS OF ENVELOPE PROTEIN OF DENGUE VIRUS BOUND WITH SQUALENE, A PROTOTYPE ANTI-VIRAL COMPOUND
DOI:
https://doi.org/10.22159/ijpps.2019v11i1.29714Keywords:
Anti-viral compounds, Dengue Virus, E protein, Molecular Dockings, SqualeneAbstract
Objective: The objective of the work was to validate the structural binding affinity of Squalene with the envelope protein of Dengue virus by means of molecular simulations.
Methods: Three-dimensional (3D) structure of dengue 2 virus envelope protein was retrieved from Protein Data Bank PDB and Squalene compound from the ZINC database. Molecular docking between the E protein and Squalene were carried out by means of Auto Dock 4.2.
Results: Based on the study, it was observed that the binding/docking energy for the complex structure was calculated to be-5.55 kcal/mol. Critical residues to interact with E protein were scrutinized by analyzing the interface of the complex within 4 Å proximity. Residues such as Thr 48, Glu49, Ala 50, Val 130, Leu 135, Ser 186, Pro 187, Thr 189, Gly 190, Leu 191, Phe 193, Leu 198, Leu 207, Thr 268, Phe 279, Thr 280, Gly 281, His 282 and Leu 283 were found to be non-covalently located around the squalene.
Conclusion: Scopes to design de novo anti-viral compounds to the dengue viruses by using squalene as a new class of template structure have also been concisely brought into fore.
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References
Kenneth M Boyd. Disease, illness, sickness, health, healing and wholeness: exploring some elusive concepts. J Med Ethics: Medical Humanities 2000;26:9–17.
World Health Organization. Neglected Tropical Diseases. Program; 2017. Available from: http://www.who.int/ neglected_diseases/en. [Last accessed on 10 Aug 2018]
Amal Mitra, Anthony Mawson. Neglected tropical diseases: epidemiology and global burden. Trop Med Infec Dis 2017;2:36.
Castilla, Luana Piccini, Elsa B Damonte. Dengue virus entry and trafficking: perspectives as antiviral target for prevention and therapy. Future Virol 2015;10:625–45.
Low, Eng Eong Ooi, Subhash G Vasudevan. Current status of dengue therapeutics research and development. J Infect Dis 2017;215 (Suppl 2):S96-S102.
Carrington LB, Simmons CP. Human to mosquito transmission of dengue viruses. Front Immunol 2014;5:290.
Rushika Perera, Richard J Kuhn. Structural proteomics of dengue virus. Curr Opin Microbiol 2008;11:369–77.
Laura A Byk, Andrea V Gamarnik. Properties and functions of the dengue virus capsid protein. Annu Rev Virol 2016;29:263–81.
Modis Y, Ogata S, Clements D, Harrison SC. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci USA 2003;100:6986–91.
Rajkuberan C, Sathishkumar G, Prabukumar P, Muthukumar K, Sivaramakrishnan S. Intrinsic studies of Euphorbia antiquorum L. latex extracts against human bacterial pathogens and mosquito vector Aedes aegypti, Culex quinquefasciatus (Diptera: Culicidae). Biocatal Agric Biotechnol 2017;10:75–82.
Irwin, Sterling, Mysinger, Bolstad, Coleman. ZINC: a free tool to discover chemistry for biology. J Chem Inf Model 2012;52:1757–68.
Morris GM. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 1998;19:1639-62.
Qian Xie, Bao Zhang, Jian Hai Yu, Qinghua Wu, Fangji Yang, Hong Cao, et al. Structure and function of the non-structural protein of dengue virus and its applications in antiviral therapy. Curr Top Med Chem 2017;17:3.
Sivakumar D, Sivaraman T. In silico designing and screening of lead compounds to NS5-methyltransferase of dengue viruses. Med Chem 2011;7:655-62.
Qamar, Arooj Mumtaz, Rabbia Naseem, Amna Ali, Tabeer Fatima, Tehreem Jabbar, et al. Molecular docking based screening of plant flavonoids as dengue NS1 inhibitors. Bioinformation 2014;10:460-5.
Ariza Leidy Lorena Garcia, Germán Alberto Tellez Ramirez. Molecular cloning, modelling and docking with curcumin of the dengue virus 2 NS5 polymerase domain. LF Castillo. eds. Advances in computational biology, advances in intelligent systems and computing 232. Springer International Publishing Switzerland; 2014.
Rufaidah Othman, Rozana Othman, Aida Baharuddin, Nagasundara Ramanan Ramakrishnan, Noorsaadah Abd Rahman, Rohana Yusof, et al. Molecular docking studies of selected medicinal drugs as dengue virus-2 protease inhibitors. Sains Malaysiana 2017;46:1865–75.
Nasution Aini, Tambunan. Virtual screening of commercial cyclic peptides as NS2B-NS3 protease inhibitor of dengue virus serotype 2 through molecular docking simulation. IOP Conf Series: Materials Science and Engineering; 2017. p. 188.
Joe Grove, Mark Marsh. The cell biology of receptor-mediated virus entry. J Cell Biol 2011;195:1071–82.
Asif Mir, Humaira Ismatullah, Sobiah Rauf, Umar Niazi. Identification of bioflavonoid as fusion inhibitor of dengue virus using molecular docking approach. Informatics Medicine Unlocked 2016;3:1–6.
Parikesit AA, Kinanty Tambunan US. Screening of commercial cyclic peptides as inhibitor envelope protein dengue virus (DENV) through molecular docking and molecular dynamics. Pak J Biol Sci 2013;16:1836.
Lin MH. Membrane undulation induced by NS4A of Dengue virus: a molecular dynamics simulation study. J Biomol Struct Dyn 2014;32:1552.
Duraisamy Gomathi, Manokaran Kalaiselvi, Ganesan Ravikumar, Kanakasabapathi Devaki, Chandrasekar Uma. GC-MS analysis of bioactive compounds from the whole plant ethanolic extract of Evolvulusalsinoides (L.) L. J Food Sci Technol 2015:52;1212–7.
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