Molecular docking based screening of neem-derived compounds with the NS1 protein of Influenza virus

Abstract

Different strains of influenza virus are affecting a large number of people worldwide to combat with Influenza virus destruction, numerous synthetic antiviral medicines are available for influenza virus in the market. But still there was a need for the development of drug which will target all the strains of influenza virus. For this purpose conserved residues within the influenza virus NS1 protein have been found by aligning all the available sequences of existing strains from the national center of biotechnology information(NCBI) protein database. The compounds from leaf extracts of neem (Azadirachta indica), previously known to have antiviral properties, were virtually screened to identify side effects free natural drug. Molecular docking identified eight potential compounds (Tetratriacontane, 127-40-2, 6-o-ACETYLNIMBANDIOL, Rutin, Tiplasinin, Hyperoside, ( )- Nimocinolide and Quercitrin) found to have perfect binding with reported conserved residues (R19, R35, S42 and D39) of influenza virus NS1 protein involved in the binding of drugs. From, further analysis 6-o-ACETYLNIMBANDIOL, Rutin and Tiplasinin were found as drug against influenza strains because their binding residues were conserved in all strains. The potential of neem chemical against influenza virus has best been highlighted through this study and it provides direction for further consideration of these products for in-vivo and in-vitro validations.

Abbreviations: NS1 protein - Non Structural 1 protein, NA - Neuraminidase, HA - Hemagglutinin, M - Yersinia enterocolitica 8081, ypk - Yersinia pestis KIM, yps - Yersinia pseudotuberculosis Db1, KEGG - Kyoto Encyclopedia of Genes and Genomes, KO - KEGG Orthology, KOBAS - KO Based Annotation System.

Keywords: Influenza virus; Molecular docking; NS1 protein; Neem leaf extract.

Figure 1

NS1 effector domain structure and legends attached to the model, taken from PDB with PDB ID (2GX9)

Figure 2

Multiple sequence alignment of influenza virus NS1 protein consensus sequences of each strain (i.e. H5N1, H7N2, H7N3, H9N2, H7N7, H1N1, H2N3, H1N2 and H2N2) using CLC Genomics Workbench 8. For the development of each consensus sequence, all the available NS1 protein sequences of the above said strains were retrieved from NCBI database and were converted to consensus sequences using CLC Genomics Workbench 8. The colored bars at the bottom are representing the conservation level. Conservation was 43 %.

Figure 3

Interaction diagrams of phytochemicals from neem leaf extract compound with influenza virus NS1 protein. Where; 1A & 1B are two dimensional and three dimensional interaction diagrams of R21, V18, W16 and C13 residues of influenza virus NS1 protein with Tetratriacontane, respectively; 2A & 2B are showing the interaction of R19, R44, and D39 residues of NS1 protein with 127-40-2, 3A and 3B part of the diagram is illustrating the binding between R19 residue with 6-o-ACETYLNIMBANDIOL. Furthermore, 4A and 4B is illuminating quercitrin and R19, S42 residue interactions, 5A and 5B shows Tiplasinin, 6A and 6B shows Hyperoside, 7A and 7B showing RUTIN, 8A and 8B is showing ( )-Nimocinolide interaction with NS1 protein residues. Interaction diagrams were attained by using ligand interaction analysis feature of MOE