Toxicology International (Formerly Indian Journal of Toxicology)

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Ligand-based Virtual Screening, Quantum Mechanics Calculations, and Normal Mode Analysis of Phytochemical Compounds Targeting Toll‐Interacting Protein (Tollip) Against Bacterial Diseases


Affiliations
1 Department of Fisheries, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
2 Department of Animal Sciences, CAU, Imphal – 795004, Manipur, India
3 ICAR-NEH Region, Manipur Centre, Lamphelpat – 795004, Manipur, India
4 Department of Environmental Science and Technology, Faculty of Applied Science, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
5 Infectious Diseases, Department of Animal Medicine, Faculty of Veterinary Medicine, Zagazig University, Zagazig City – 44511, Sharkia Province, Egypt
     

   Subscribe/Renew Journal


The Labeo rohita (Rohu) Toll interacting protein (Tollip) is ubiquitously expressed in the kidneys, gills, spleen, liver, and blood. Tollip in L. rohita has higher eukaryotic structural features and is produced in response to bacterial infections. Several bacterial diseases, such as Aeromonas hydrophila and Vibrio spp, have been reported in the internal organs of L. rohita. The consequences of these bacterial infections can be 100% mortality of fish. There are currently no medicines or vaccines available to prevent or treat infections caused by the involvement of this protein. During bacterial infections, it was discovered that Tollip plays an essential function as a negative regulator of the MyD88-dependent TLR signalling pathway. Therefore, the study aimed to evaluate the inhibitory potentiality of the Allium sativum compound against Tollip. A. sativum has been reported to show potential antibacterial activity against numerous microbial pathogens. Still, activity against the Tollip-promoted pathogens has not yet been reported. In silico virtual screen and molecular docking methods were used in this study to calculate the binding affinity of 48 drug compounds of A. sativum against the receptor Tollip. The docking and normal mode analysis methods predict 2 (PubChem CID: 122130381 and CID 12303662) inhibitory compounds that bind strongly with the Tollip with a binding affinity of -9.2 and -8.8 kcal/mol, respectively. The ADMET properties of the compounds also verified the drug resemblance features of the two compounds of A. sativum. Furthermore, to evaluate the efficacy of these two potential inhibitors, more in-vitro testing is required.

Keywords

Allium sativum, ADMET, Bacteria, Docking, Tollip
User
Subscription Login to verify subscription
Notifications
Font Size

  • Huang R, Lv J, Luo D, Liao L, Zhu Z, Wang Y. Identification, characterization and the interaction of Tollip and IRAK-1 in grass carp (Ctenopharyngodon idellus). Fish and Shellfish Immunology. 2012; 33(3):459–67. PMid: 22659441. https://doi.org/10.1016/j.fsi.2012.05.025

  • Shan S, Wang L, Zhang F, Zhu Y, An L, Yang G. Characterization and expression analysis of Toll-interacting protein in common carp, Cyprinus carpio L., responding to bacterial and viral challenge. SpringerPlus. 2016; 5(1):1– 10. PMid: 27330905 PMCid: PMC4870529. https://doi. org/10.1186/s40064-016-2293-3

  • Lu Y, Li C, Wang D, Su X, Jin C, Li Y, et al. Characterization of two negative regulators of the Toll-like receptor pathway in Apostichopus japonicus: Inhibitor of NF-κB and Tollinteracting protein. Fish and Shellfish Immunology. 2013; 35(5):1663–9. PMid: 23978566. https://doi.org/10.1016/j. fsi.2013.08.014

  • Jalil A, Ashfaq UA, Shahzadi S, Javed MR, Rasul I, Rehman S-u, et al. Screening and design of antidiabetic compounds sourced from the leaves of neem (Azadirachta indica). Bioinformation. 2013; 9(20):1031. PMid: 24497731 PMCid: PMC3910360. https://doi.org/10.6026/97320630091031

  • Srivastava AK, Maurya R. Antihyperglycemic activity of compounds isolated from Indian medicinal plants. 2010.

  • El-Saber Batiha G, Magdy Beshbishy A, G. Wasef L, Elewa YH, A. Al-Sagan A, Abd El-Hack ME, et al. Chemical constituents and pharmacological activities of garlic (Allium sativum L.): A review. Nutrients. 2020; 12(3):872. PMid: 32213941 PMCid: PMC7146530. https://doi.org/10.3390/ nu12030872 7. Labh S, Shakya S. Medicinal uses of garlic (Allium sativum) improves fish health and acts as an immunostimulant in aquaculture. 2014; 2:44–7.

  • Lim SM, Xie T, Westover KD, Ficarro SB, Tae HS, Gurbani D, et al. Development of small molecules targeting the pseudokinase Her3. Bioorganic and Medicinal Chemistry Letters. 2015; 25(16):3382–9. PMid: 26094118 PMCid: PMC4633287. https://doi.org/10.1016/j.bmcl.2015.04.103

  • Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. British Journal of Pharmacology. 2011; 162(6):1239–49. PMid: 21091654 PMCid: PMC3058157. https://doi.org/10.1111/j.1476-5381.2010.01127.x

  • Szymański P, Markowicz M, Mikiciuk-Olasik E. Adaptation of high-throughput screening in drug discovery-toxicological screening tests. International Journal of Molecular Sciences. 2011; 13(1):427–52. PMid: 22312262 PMCid: PMC3269696. https://doi.org/10.3390/ijms13010427

  • Kumar V, Jung Y-S, Liang P-H. Anti-SARS coronavirus agents: a patent review (2008-present). Expert opinion on therapeutic patents. 2013; 23(10):1337–48. PMid: 23905913. https://doi.org/10.1517/13543776.2013.823159

  • Wichapong K, Nueangaudom A, Pianwanit S, Sippl W, Kokpol S. Identification of potential hit compounds for Dengue virus NS2B/NS3 protease inhibitors by combining virtual screening and binding free energy calculations. Trop Biomed. 2013; 30(3):388–408.

  • Islam S, Mou M, Sanjida S, Mahfuj MsE. An In-silico Approach for Identifying Phytochemical Inhibitors Against Nervous Necrosis Virus (NNV) in Asian Sea Bass by Targeting Capsid Protein. Genetics of Aquatic Organisms. 2022; 6:487. https://doi.org/10.4194/GA487

  • Islam S, Mou M. Functional Annotation of Uncharacterized Protein from Photobacterium damselae subsp. piscicida (Pasteurella piscicida) and Comparison of Drug Target Between Conventional Medicine and Phytochemical Compound Against Disease Treatment in Fish: An In-silico Approach. Genetics of Aquatic Organisms. 2022; 6:453. https://doi.org/10.4194/GA453

  • Wu J, Hu B, Sun X, Wang H, Huang Y, Zhang Y, et al. In silico study reveals existing drugs as α-glucosidase inhibitors: Structure-based virtual screening validated by experimental investigation. Journal of Molecular Structure. 2020; 1218:128532. https://doi.org/10.1016/j. molstruc.2020.128532

  • Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B. 2020; 10(5):766–88. PMid: 32292689 PMCid: PMC7102550. https://doi.org/10.1016/j. apsb.2020.02.008

  • Islam S, Sanjida S, Mahfuj MsE, Islam MJ, Mou M. Computer-aided drug design of Azadirachta indica compounds against nervous necrosis virus by targeting grouper heat shock cognate protein 70 (GHSC70): Quantum mechanics calculations and molecular dynamic simulation approaches. Genomics and Informatics. 2022;20. PMid: 36239110 PMCid: PMC9576468. https://doi.org/10.5808/ gi.21063

  • Sanjida S, Mou M, Islam S, Mahfuj MsE. Identification of potential antiviral drug compound against Erythrocytic necrosis virus by targeting Major capsid protein. International Journal of Life Sciences and Biotechnology. 2022. https://doi.org/10.38001/ijlsb.1074392

  • Combet C, Blanchet C, Geourjon C, Deleage G. NPS@: Network protein sequence analysis. Trends in Biochemical Sciences. 2000; 25(3):147–50. PMid: 10694887. https://doi.org/10.1016/S0968-0004(99)01540-6

  • Xu J, Mcpartlon M, Li J. Improved protein structure prediction by deep learning irrespective of co-evolution information. Nature Machine Intelligence. 2021; 3(7):601– 9. PMid: 34368623 PMCid: PMC8340610. https://doi. org/10.1038/s42256-021-00348-5

  • Islam S, Mou M, Sanjida S, Mahfuj MsE, Alam M, Ara Y. An In-silico analysis of the molecular interactions between PmCBP-VP24 and PmCBP-VP28 protein complex to understand the initial initiating events of shrimp WSSV infection. International Journal of Life Sciences and Biotechnology. 2022. https://doi.org/10.38001/ijlsb.1055840

  • Islam S, Mou M, Sanjida S, Mahfuj MsE. Functional annotation and characterization of a hypothetical protein from Pseudoalteromonas spp. Identify Potential Biomarker: An In-silico Approach. Aquatic Food Studies. 2022; 2:57. DOI: 10.5281/zenodo.6589947 https://doi.org/10.4194/AFS57

  • Sanjida S, Mou MJ, Islam SI, Sarower-E-Mahfuj M. An In-silico approaches for identification of potential natural antiviral drug candidates against Erythrocytic necrosis virus (Iridovirus) by targeting Major capsid protein: A Quantum mechanics calculations approach. International Journal of Life Sciences and Biotechnology. 2022: 294–315. https://doi.org/10.38001/ijlsb.1074392

  • Wiederstein M, Sippl MJ. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic acids research. 2007; 35(suppl_2):W407–W10. PMid:175: PMC1933241. https://doi.org/10.1093/nar/gkm290

  • Ramachandran GN, Ramakrishnan C, Sasisekharan V. Stereochemistry of polypeptide chain configurations. J mol Biol. 1963; 7:95–9. PMid: 13990617. https://doi.org/10.1016/S0022- 2836(63)80023-6

  • Islam SI, Sanjida S, Mou MJ, Sarower-E-Mahfuj M, Nasir S. In-silico functional annotation of a hypothetical protein from Edwardsiella tarda revealed Proline metabolism and apoptosis in fish. International Journal of Life Sciences and Biotechnology. 2022; 5(1):78–96. https://doi.org/10.38001/ ijlsb.1032171

  • Islam SI, Jahan MM. Functional annotation of uncharacterized protein from photobacterium damselae subsp. piscicida (pasteurella piscicida) and comparison of drug target between conventional medicine and phytochemical compound against disease treatment in fish: An In-silico Approach. Genetics of Aquatic Organisms. 2022; 6(3). https://doi.org/10.4194/GA453

  • Mohanraj K, Karthikeyan BS, Vivek-Ananth R, Chand R, Aparna S, Mangalapandi P, et al. IMPPAT: A curated database of Indian medicinal plants, phytochemistry and therapeutics. Scientific reports. 2018; 8(1):1–17. PMid: 29531263 PMCid: PMC5847565. https://doi.org/10.1038/ s41598-018-22631-z

  • Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Chemical Biology: Springer; 2015. p. 243–50. PMid: 25618350. https://doi.org/10.1007/978-1- 4939-2269-7_19

  • Li Y, Meng Q, Yang M, Liu D, Hou X, Tang L, et al. Current trends in drug metabolism and pharmacokinetics. Acta Pharmaceutica Sinica B. 2019; 9(6):1113–44. PMid: 31867160 PMCid: PMC6900561. https://doi.org/10.1016/j. apsb.2019.10.001

  • Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports. 2017; 7(1):1–13. PMid: 28256516 PMCid: PMC5335600. https://doi.org/10.1038/srep42717

  • Li C, Wang J, Wang Y, Gao H, Wei G, Huang Y, et al. Recent progress in drug delivery. Acta pharmaceutica sinica B. 2019; 9(6):1145–62. PMid: 31867161 PMCid: PMC6900554. https://doi.org/10.1016/j.apsb.2019.08.003

  • Friesner RA, Guallar V. Ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (QM/ MM) methods for studying enzymatic catalysis. Annual Review of Physical Chemistry. 2005; 56:389. PMid: 15796706. https://doi.org/10.1146/annurev.physchem. 55.091602.094410

  • Maity A, Samanta S, Biswas D, Chakravorty D. Studies on nanoconfinement effect of NiO-SiO2 spin glass within mesoporous Al2O3 template. Journal of Alloys and Compounds. 2021; 887:161447. https://doi.org/10.1016/j.jallcom.2021.161447

  • Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics. 2012; 4(1):1–17. PMid: 22889332 PMCid: PMC3542060. https://doi.org/10.1186/1758-2946- 4-17

  • Li Y, Evans JN. The Fukui function: A key concept linking frontier molecular orbital theory and the hard-soft-acidbase principle. Journal of the American Chemical Society. 1995; 117(29):7756–9. https://doi.org/10.1021/ja00134a021

  • Pandey RK, Verma P, Sharma D, Bhatt TK, Sundar S, Prajapati VK. High-throughput virtual screening and quantum mechanics approach to develop imipramine analogues as leads against trypanothione reductase of leishmania. Biomedicine and Pharmacotherapy. 2016; 83:141–52. PMid: 27470561. https://doi.org/10.1016/j.biopha.2016.06.010 38. López-Blanco JR, Aliaga JI, Quintana-Ortí ES, Chacón P. iMODS: Internal coordinates normal mode analysis server. Nucleic Acids Research. 2014; 42(W1):W271–W6. PMid: 24771341 PMCid: PMC4086069. https://doi.org/10.1093/nar/gku339

  • Bharadwaj S, Dubey A, Yadava U, Mishra SK, Kang SG, Dwivedi VD. Exploration of natural compounds with anti- SARS-CoV-2 activity via inhibition of SARS-CoV-2 Mpro. Briefings in bioinformatics. 2021; 22(2):1361–77. PMid: 33406222 PMCid: PMC7929395. https://doi.org/10.1093/ bib/bbaa382

  • Miar M, Shiroudi A, Pourshamsian K, Oliaey AR, Hatamjafari F. Theoretical investigations on the HOMOLUMO gap and global reactivity descriptor studies, natural bond orbital, and nucleus-independent chemical shifts analyses of 3-phenylbenzo [d] thiazole-2 (3 H)-imine and its para-substituted derivatives: Solvent and substituent effects. Journal of Chemical Research. 2021; 45(1-2):147– 58. https://doi.org/10.1177/1747519820932091

  • Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021; 6(1):291. PMid: 34344870 PMCid: PMC8333067. https://doi.org/10.1038/ s41392-021-00687-0

  • Zhang J, Kong X, Zhou C, Li L, Nie G, Li X. Toll-like receptor recognition of bacteria in fish: ligand specificity and signal pathways. Fish Shellfish Immunol. 2014; 41(2):380–8. PMid: 25241605. https://doi.org/10.1016/j.fsi.2014.09.022

  • Gerold G, Zychlinsky A, de Diego JL. What is the role of Toll-like receptors in bacterial infections? Semin Immunol. 2007; 19(1):41–7. PMid: 17280841. https://doi. org/10.1016/j.smim.2006.12.003

  • Mohanty A, Sadangi S, Paichha M, Saha A, Das S, Samanta M. Toll-interacting protein in the freshwater fish Labeo rohita exhibits conserved structural motifs of higher eukaryotes and is distinctly expressed in pathogenassociated molecular pattern stimulations and bacterial infections. Microbiol Immunol. 2021; 65(8):281–9. PMid: 32237168. https://doi.org/10.1111/1348-0421.12792

  • Ramesh D, Souissi S. Antibiotic resistance and virulence traits of bacterial pathogens from infected freshwater fish, Labeo rohita. Microb Pathog. 2018; 116:113–9. PMid: 29339308. https://doi.org/10.1016/j.micpath.2018.01.019

  • Mohanty A, Sadangi S, Paichha M, Saha A, Das S, Samanta M. Toll-interacting protein in the freshwater fish Labeo rohita exhibits conserved structural motifs of higher eukaryotes and is distinctly expressed in pathogen-associated molecular pattern stimulations and bacterial infections. Microbiology and Immunology. 2021; 65(8):281–9. PMid: 32237168. https://doi.org/10.1111/1348-0421.12792

  • Chakraborty SB, Horn P, Hancz C. Application of phytochemicals as growth‐promoters and endocrine modulators in fish culture. Reviews in Aquaculture. 2014; 6(1):1–19. https://doi.org/10.1111/raq.12021

  • Valenzuela-Gutiérrez R, Lago-Lestón A, Vargas-Albores F, Cicala F, Martínez-Porchas M. Exploring the garlic (Allium sativum) properties for fish aquaculture. Fish Physiol Biochem. 2021; 47(4):1179–98. PMid: 34164770. https://doi.org/10.1007/s10695-021-00952-7

  • Madhavi Sastry G, Adzhigirey M, Day T, Annabhimoju R, Sherman W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design. 2013; 27(3):221–34. PMid: 23579614. https://doi.org/10.1007/s10822-013-9644-8

  • Islam S, Mou M. Analysis of a Hypothetical Protein from Vibrio Harveyi Identified Possible Connection with Biopolymer Metabolism: An In-Silico Approach. Journal of Applied Biological Sciences. 2022; 16:191–205. DOI: 10.5281/zenodo.6589947

  • Islam S, Sanjida S, Mou M, Mahfuj MsE, Nasir S. In-silico functional annotation of a hypothetical protein from Edwardsiella tarda revealed Proline metabolism and apoptosis in fish. International Journal of Life Sciences and Biotechnology. 2022; 5:78–96. https://doi.org/10.38001/ ijlsb.1032171

  • Lipinski CA. Lead- and drug-like compounds: The ruleof- five revolution. Drug Discov Today Technol. 2004; 1(4):337–41. PMid: 24981612. https://doi.org/10.1016/j. ddtec.2004.11.007

  • Pollastri MP. Overview on the Rule of Five. Curr Protoc Pharmacol. 2010; Chapter 9: Unit 9.12. PMid: 22294375. https://doi.org/10.1002/0471141755.ph0912s49

  • Aljahdali MO, Molla MHR, Ahammad F. compounds identified from marine mangrove plant (Avicennia alba) as potential antiviral drug candidates against WDSV, an In-Silico Approach. Mar Drugs. 2021; 19(5). PMid: 33925208 PMCid: PMC8145693. https://doi.org/10.3390/ md19050253


Abstract Views: 257

PDF Views: 0




  • Ligand-based Virtual Screening, Quantum Mechanics Calculations, and Normal Mode Analysis of Phytochemical Compounds Targeting Toll‐Interacting Protein (Tollip) Against Bacterial Diseases

Abstract Views: 257  |  PDF Views: 0

Authors

Sk Injamamul Islam
Department of Fisheries, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
M. Norjit Singh
Department of Animal Sciences, CAU, Imphal – 795004, Manipur, India
C. Sonia
ICAR-NEH Region, Manipur Centre, Lamphelpat – 795004, Manipur, India
Md Akib Ferdous
Department of Fisheries, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
Nasim Habib
Department of Fisheries, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
Saloa Sanjida
Department of Environmental Science and Technology, Faculty of Applied Science, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
Md Jamadul Islam
Department of Fisheries, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
Nahidul Islam
Department of Fisheries, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore – 7408, Bangladesh
Mohamed H Hamad
Infectious Diseases, Department of Animal Medicine, Faculty of Veterinary Medicine, Zagazig University, Zagazig City – 44511, Sharkia Province, Egypt

Abstract


The Labeo rohita (Rohu) Toll interacting protein (Tollip) is ubiquitously expressed in the kidneys, gills, spleen, liver, and blood. Tollip in L. rohita has higher eukaryotic structural features and is produced in response to bacterial infections. Several bacterial diseases, such as Aeromonas hydrophila and Vibrio spp, have been reported in the internal organs of L. rohita. The consequences of these bacterial infections can be 100% mortality of fish. There are currently no medicines or vaccines available to prevent or treat infections caused by the involvement of this protein. During bacterial infections, it was discovered that Tollip plays an essential function as a negative regulator of the MyD88-dependent TLR signalling pathway. Therefore, the study aimed to evaluate the inhibitory potentiality of the Allium sativum compound against Tollip. A. sativum has been reported to show potential antibacterial activity against numerous microbial pathogens. Still, activity against the Tollip-promoted pathogens has not yet been reported. In silico virtual screen and molecular docking methods were used in this study to calculate the binding affinity of 48 drug compounds of A. sativum against the receptor Tollip. The docking and normal mode analysis methods predict 2 (PubChem CID: 122130381 and CID 12303662) inhibitory compounds that bind strongly with the Tollip with a binding affinity of -9.2 and -8.8 kcal/mol, respectively. The ADMET properties of the compounds also verified the drug resemblance features of the two compounds of A. sativum. Furthermore, to evaluate the efficacy of these two potential inhibitors, more in-vitro testing is required.

Keywords


Allium sativum, ADMET, Bacteria, Docking, Tollip

References





DOI: https://doi.org/10.18311/ti%2F2023%2Fv30i2%2F30768