Designing and screening of universal drug from neem (Azadirachta indica) and standard drug chemicals against influenza virus nucleoprotein

Aftab Ahmad, Muhammad Rizwan Javed, Abdul Qayyum Rao, Tayyab Husnain, Aftab Ahmad, Muhammad Rizwan Javed, Abdul Qayyum Rao, Tayyab Husnain

Abstract

Background: Different strains of influenza virus are affecting a large number of people worldwide. Many synthetic antiviral medicines are available for influenza virus in the market. But still there is a need for the development of universal drugs against these strains of influenza virus.

Methods: For this purpose conserved residues within the influenza virus nucleoprotein have been retrieved. The drugs, previously known to have antiviral properties, were screened to identify the best candidate universal drug against Influenza virus strains. Compounds from leaf extracts of neem, were also screened to identify the natural drugs without side effects.

Result: Molecular docking identified three potential compounds (Nimbaflavone, Rutin, and Hyperoside) having perfect binding with reported conserved residues (ASP302, SER50) of influenza virus nucleoprotein that is involved in the binding of drugs. Further analysis showed Hyperoside as a universal drug against various influenza strains. Some chemical drugs were also evaluated through screening against nucleoprotein. The results showed six drugs (OMS, CBX, LGH, Naproxen, BMS-883559, and BMS-885838) which were interacting with same conserved residues (ASP302, TYR52, SER50, GLY288, SER376, and ARG99) as were found in the case of neem phytochemicals. Hyperoside from neem leaf extract along with drugs LGH, Naproxen, BMS-885838, and BMS-883559 showed best interactions with conserved residues of nucleoprotein.

Conclusion: The compound Hyperoside from neem leaf extract along with drugs LGH, Naproxen, BMS-885838, and BMS-883559 showed best interactions with conserved residues of nucleoprotein. So these compounds have been identified for their potential against influenza strains to be utilized as a universal drug.

Keywords: Influenza virus; Molecular docking; Neem leaf extract; Nucleoprotein; Universal drug.

Figures

Fig. 1
Fig. 1
Multiple sequence alignment of influenza virus nucleoprotein 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 nucleoprotein sequences of 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 %age
Fig. 2
Fig. 2
Interaction diagrams of phytochemicals from Neem leaf extract compounds with influenza virus nucleoprotein. Where; 1A & 1B are two dimensional and three dimensional interaction diagrams of ARG305, TYR289, TYR52 and ASP302 residues of influenza virus nucleoprotein with Nimbaflavone, respectively; 2A & 2B are showing the interaction of ARG305, TYR289, ASP302, SER50 and GLY288 residues of nucleoprotein with Rutin; and 3A & 3B are illustrating the interaction of ASN309, TYR289 and TYR52 residues with Hyperoside. Interaction diagrams were attained by using ligand interaction analysis feature of MOE
Fig. 3
Fig. 3
Interaction diagrams of reported drugs with influenza virus nucleoprotein. Whereas; 1A & 1B are showing binding of OMS with ARG305, ASN309; 2A & 2B are illustrating CBX interactions with ARG305, ASN309; 3A & 3B are showing interactions of LGH with TYR52, GLY288 residues of nucleoprotein, respectively. Furthermore, 4A & 4B are describing naproxen interactions with ARG99, TYR52, SER376 residues; While 5A & 5B of BMS-883559; 6A of BMS-885838; and 6B of BMS-885838, respectively. Interaction diagrams were attained by using ligand interaction analysis feature of MOE

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