Computational screening of phytochemicals to discover potent inhibitors against chinkungunya virus

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Research Articles | Published:

Print ISSN : 0970-4078.
Online ISSN : 2229-4473.
Website:www.vegetosindia.org
Pub Email: contact@vegetosindia.org
Doi: 10.1007/s42535-021-00227-9
First Page: 515
Last Page: 527
Views: 1288


Keywords: Chikungunya virus (CHIKV), In silico screening, Molecular dynamic simulation, Phytochemicals


Abstract


Even with the advancement in the field of medicine, currently, there are no permanent cures available to combat the Chikungunya virus (CHIKV) infection, and the only therapy being used is symptomatic treatment. Therefore, there is an exigency to find out potential drug candidates against CHIKV infection. Authors administered in silico screening to check the antiviral potency of phytochemicals against the envelope protein of CHIKV, which is a promising target to inhibit viral entry. Screening of various phytochemicals with respect to pathophysiological importance was performed, followed by ADME evaluations to study the pharmacokinetic properties and drug-like nature of the selected compounds. The molecules were filtered through a process of docking studies and toxicity analysis, which implied Withaferin-A to be safe among the others. Furthermore, the molecular dynamic simulation studies, considering RMSD, RMSF, Radius of Gyration (Rg), and H-bonding of the receptor-ligand complexes, manifested E1-E2 glycoprotein-Withaferin-A complex as stable, hence making it a promising drug candidate. It is hoped that this study could provide valuable cues for the development of broad-spectrum natural anti-CHIKV therapy.


Chikungunya virus (CHIKV), In silico screening, Molecular dynamic simulation, Phytochemicals


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References


  1. Abraham M, James T, Murtola R, Schulz S, Páll S, Smith JC, Hess B, Lindahl E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2:19–25. https://doi.org/10.1016/j.softx.2015.06.001

  2. Agarwal G (2019) Virtual screening of inhibitors against envelope glycoprotein of chikungunya virus: a drug repositioning approach. Bioinformation 15(6):439–447. https://doi.org/10.6026/97320630015439

  3. Banerjee P, Eckert AO, Schrey AK (2018) ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 46(W1):W257–W263. https://doi.org/10.1093/nar/gky318

  4. Bitencourt-Ferreira V, Veit-Acosta M, de Azevedo WF Jr (2019) Hydrogen bonds in protein-ligand complexes. Methods Mol Biol (Clifton, N.J.) 2053:93–107. https://doi.org/10.1007/978-1-4939-9752-7_7

  5. Dahlgren D, Lennernäs Hans (2019) Intestinal permeability and drug absorption: predictive experimental, computational and in vivo approaches. Pharmaceutics. https://doi.org/10.3390/pharmaceutics11080411

  6. Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7(January):1–13. https://doi.org/10.1038/srep42717

  7. Delogu I, Pastorino B, Baronti C, Nougairède A, Bonnet E, Xavier de Lamballerie (2011) In vitro antiviral activity of arbidol against chikungunya virus and characteristics of a selected resistant mutant. Antiviral Res 90(3):99–107. https://doi.org/10.1016/j.antiviral.2011.03.182

  8. van Duijl-Richter, Mareike KS, Hoornweg TE, Izabela A, Rodenhuis-Zybert, Smit JM (2015) Early events in chikungunya virus infection—from virus cell binding to membrane fusion. Viruses 7(7):3647–3674. https://doi.org/10.3390/v7072792

  9. Garg S, Anand A, Lamba Y (2020) Molecular docking analysis of selected phytochemicals against SARS-CoV-2 Mpro receptor. Vegetos 33(4):766–781. https://doi.org/10.1007/s42535-020-00162-1

  10. Keiser MJ (2015) In silico prediction of drug side effects. Antitargets Drug Safety. https://doi.org/10.1002/9783527673643.ch02

  11. Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q et al (2020) PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res 49(D1):D1388–D1395. https://doi.org/10.1093/nar/gkaa971

  12. Leeson PD (2007) The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discovery 6(11):881–890. https://doi.org/10.1038/nrd2445

  13. Morris GM, Ruth H, Lindstrom W, Michel F, Sanner RK, Belew DS, Goodsell (2009) Software news and updates AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30(16):2785–2791. https://doi.org/10.1002/jcc.21256

  14. Oo A, Rausalu K, Merits A, Higgs S, Vanlandingham D, Bakar SA (2018) Deciphering the potential of baicalin as an antiviral agent for chikungunya virus infection. Antiviral Res 150(February):101–111. https://doi.org/10.1016/j.antiviral.2017.12.012

  15. Parashar D, Cherian S (2014) Antiviral perspectives for chikungunya virus. BioMed Res Int. https://doi.org/10.1155/2014/631642

  16. Pohjala L, Utt A, Varjak M, Lulla A, Merits A, Ahola T, Päivi Tammela (2011) Inhibitors of alphavirus entry and replication identified with a stable chikungunya replicon cell line and virus-based assays. PLoS ONE. https://doi.org/10.1371/journal.pone.0028923

  17. Rashad AA, Paul AK (2013) Structure based design towards the identification of novel binding sites and inhibitors for the chikungunya virus envelope proteins. J Mol Graph Model 44:241–252. https://doi.org/10.1016/j.jmgm.2013.07.001

  18. Sadowski J, Gasteiger J (1993) Comparison of automatic three-dimensional model builders using 639 x-ray structures. J Chem Inf Comput Sci 33(4):1000–1008

  19. Schüttelkopf AW, van Aalten DMF (2004) PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr 60(Pt 8):1355–1363. https://doi.org/10.1107/S0907444904011679

  20. Schwab CH (2010) Conformations and 3D pharmacophore searching. Drug Discov Today Technol 7(4):e245–e253. https://doi.org/10.1016/j.ddtec.2010.10.003

  21. Sharma P, Joshi T, Joshi T, Chandra S (2020) Molecular dynamics simulation for screening phytochemicals as α-amylase inhibitors from medicinal plants. J Biomol Struct Dyn 0(0):1–15. https://doi.org/10.1080/07391102.2020.1801507

  22. Varghese FS, Rausalu K, Hakanen M, Saul S, Kümmerer BM, Susi P, Merits A (2017) Obatoclax inhibits alphavirus membrane fusion by neutralizing the acidic environment of endocytic compartments. Antimicrob Agents Chemother 61(3):1–17. https://doi.org/10.1128/AAC.02227-16

  23. Voss JE, Vaney MC, Duquerroy S, Vonrhein C, Girard-Blanc C, Crublet E, Thompson A, Bricogne G, Félix AR (2010) Glycoprotein organization of chikungunya virus particles revealed by X-ray crystallography. Nature 468(7324):709–712. https://doi.org/10.1038/nature09555

  24. Waring MJ (2010) Lipophilicity in drug discovery. Expert Opin Drug Discov 5(3):235–248. https://doi.org/10.1517/17460441003605098

  25. Weber C, Sliva K, von Rhein C, Beate M, Kümmerer, Barbara SS (2015) The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection. Antiviral Res 113:1–3. https://doi.org/10.1016/j.antiviral.2014.11.001

  26. Wintachai P, Thuaud F, Basmadjian C, Roytrakul S, Ubol S, Désaubry L, Smith DR (2015) Assessment of flavaglines as potential chikungunya virus entry inhibitors. Microbiol Immunol 59(3):129–141. https://doi.org/10.1111/1348-0421.12230

  27. Yang H, Sun L, Li W, Liu G, Tang Y (2018) In silico prediction of chemical toxicity for drug design using machine learning methods and structural alerts. Front Chem 6(February):1–12. https://doi.org/10.3389/fchem.2018.00030


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Acknowledgements


The authors would like to thank the staff of National Facility for Biopharmaceuticals for their encouragement and advice for research work.


Author Information


Jha Vikas
National Facility for Biopharmaceuticals, Mumbai, India
vikasjjha7@gmail.com
Matharoo Darpan Kaur
Department of Five Years Integrated Course in Bioanalytical Sciences, GNIRD, G. N. Khalsa College, Mumbai, India


Kasbe Sankalp
Department of Five Years Integrated Course in Bioanalytical Sciences, GNIRD, G. N. Khalsa College, Mumbai, India


Gharat Kunal
Department of Five Years Integrated Course in Bioanalytical Sciences, GNIRD, G. N. Khalsa College, Mumbai, India


Rathod Meet
Department of Five Years Integrated Course in Bioanalytical Sciences, GNIRD, G. N. Khalsa College, Mumbai, India

Sonawane Neetu
Department of Five Years Integrated Course in Bioanalytical Sciences, GNIRD, G. N. Khalsa College, Mumbai, India

Kanade Tanvi
Department of Biological Sciences, SVKM’s NMIMS Sunadan Divatia School of Science, Mumbai, India