Toxicology International (Formerly Indian Journal of Toxicology)

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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
     

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

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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