Molecular docking NS4B of DENV 1-4 with known bioactive phyto-chemicals

Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS4B is a target for designing specific antivirals due to its importance in viral replication. Medicinal plants have been a savior for dengue virus as they consist of a class of phytochemicals having anti-viral activity and can pose a new approach ofstrong drug against viruses. The present study analyzes the activity of compounds against NS4B of DENV (1-4) serotypes. In this study Catechin, Cianidanol, Epicatechin, Eupatoretin, Glabranin, Laurifolin, DL-Catechin, astherapeutic agents were filtered by using Lipinski rule’s five and the drug-likeness property of these agents were used for assessment of pharmacological properties. The molecular docking results presented the 2-D structures of bioactive complex, which interacted with especially conserved residues of target domains. Interestingly, we find the Catechin, Laurifolin, Cianidanol have highest binding energy against NS4B in DENV-1,2,4 which is evident by the formation of more hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results revealed that the bioactive compound, especially Catechin has significant anti-dengue activities. In addition, this study may be helpful in further experimental investigations.

Currently, studies to find antiviral molecules have focused on targeting essential viral enzymes in the infection process by the direct or indirect inhibition of their biological functions or by blocking the viral replication machinery [11]. One of the most used targets that is employed for this purpose is NS4B which plays a central role in the viral life cycle; it acts as an attractive therapeutic target for antiviral compounds, essential for viral replication and infectivity [12]. Previous studies have provided considerable evidence for the importance of NS4B as potential drug target [13]. NS4B is highly hydrophobic membrane protein, which appears to have two hydrophobic segments (residues 1 to 56 and residues 56-93), which are probably associated with the ER lumen side of the membrane, and three C-terminal TM

Methodology
An investigation was carried out at laboratories, which have permitted the authors to work there to identify potential bioactive compounds using chemoinformatics and to study the binding action of compounds on molecular target and inhibitory effect on DENV 1-4.

Identification of Bioactive Compounds:
For the identification of active compounds, authors selected the available compounds from Pubchem server tools, Drug Bank and the following procedures were undertaken.

Sketch the structures of Compounds:
The structure of selected bioactive compounds was drawn with the help of Pubchem project which are freely available to use. 2-D and 3-D structures were generated by using the software and were further used for docking [16].

Using Open Babel Converting File Format:
Open Babel is free software which is used for converting the file formats.

Receptor 3D structure
The three dimensional structure of NS4B cofactor is available in the protein data bank (PDB) in the authors previous study. The three dimensional structure of NS4B of DENV 1-4 was retrieved from the protein data bank. All water molecules were removed and on the final stage hydrogen atoms were added to the target protein molecule [13]. Collections of active compounds were selected. The 2D structure of seven ligands were retrieved from the NCBI PubChem database, in addition to it all the ligand molecules were converted into 3D structure using the 3D converter module program and then energy minimized. Figure 1 shows the 3D structure of the bioactive compounds [14].

Drug-likeness Prediction
To predict the drug-likeness value molsoft web tool is used   table after molecular docking   Interaction  DENV1  DENV2  DENV3  Software predicts the molecular properties of the active compounds for different types of models and all these compounds have shown positive results as in Table 6. All the bioactive compounds have follow Lipinski's Rule depending on the molecular properties of compounds.

Drug-likeness prediction
Using molsoft web tool, we can predict the drug-likeness value.
The drug-likeness score of Catechin is 0.92, Eupatoretin is 0.70, Glabranin is 1.08 and Laurifolin is 1.10. These score indicate that all the compounds are nontoxic and can be used as drugs ( Figure   3).  The docking parameters such as hydrogen bond interactions,