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Fig 1.

A schematic diagram of the link of DENV infection with host genes/proteins.

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Table 1.

The detailed descriptions of the gene expression profile datasets.

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Fig 2.

Volcano plots and venn diagrams for hDEGs.

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Fig 3.

Selection of hKGs using eight topological measures in the PPI-network.

(A) The top 9 hKGs were selected from the PPI network.(B) Protein-protein interactions (PPIs) network analysis of commonly host differentially expressed genes (hDEGs). Nodes depicted in an octagonal shape and colored purple represent the host key genes (hKGs).

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Fig 4.

hKGs regulatory networks.

(A) TFs-hKGs interaction network, (B) miRNAs-hKGs interaction network. Here, hKGs were marked as purple with octagon shapes. The TFs and miRNAs were marked in blue and brown colors with an ellipse shape.

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Table 2.

GO terms and KEGG pathways that are significantly enriched with common hDEGs by incorporating KGs related to the pathogenetic processes of DENVI.

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Fig 5.

Image of drug-target binding affinity top 30 matrices (A) X-axis indicates top-ordered 30 drug agents (out of 183) and Y-axis indicates ordered proposed receptor proteins.

The target receptor proteins are arranged in rows, and the drug agents are listed in columns, with red colors indicating strong binding affinities. The red text in the rows signifies the proposed drug agents (selected from ADME/T analysis). (B) Proposed drugs are represented on the Y-axis, while the X-axis displays top 10 (out of 35) target proteins identified in various publications as highlighted genes for DENVI.

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Fig 6.

This figure presents the post-docking analysis and ligand-protein interactions: The first, second, and third columns illustrate potential targets, the 2D structures of lead compounds, and the top-ranked binding affinities (kcal mol1), respectively.

The fourth column presents a 3D view of the highest-ranking drug-target complexes. Last column emphasizes key aspects of the interacting amino acids.

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Table 3.

ADME/T characteristics of the top-ranked ten drugs.

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Fig 7.

The molecular orbitals of the chosen candidate drug molecules, particularly the HOMO and LUMO.

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Table 4.

Identified FMO energies together with their corresponding physicochemical descriptors, which encompass chemical hardness, electronegativity, softness, chemical potential, and the global electrophilicity index.

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Fig 8.

MD simulation results for top three complexes.

(A) The results of the RMSD analysis for a 100-nanosecond simulation involving each of the proposed three drug-target complexes, (B) The RMSF is assessed based on the average RMSF of the atoms that make up the residue, and (C) calculations of binding free energy (MM-PBSA) for the proposed three drug-target complexes.

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Fig 9.

The pipeline of this study.

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