In silico study of carvone derivatives as potential neuraminidase inhibitors

Jusoh, Noorakmar and Zainal, Hasanuddin and Abdul Hamid, Azzmer Azzar and Muhamad Bunnori, Noraslinda and Abd Halim, Khairul Bariyyah and Abd Hamid, Shafida (2018) In silico study of carvone derivatives as potential neuraminidase inhibitors. Journal of Molecular Modeling, 24 (4). pp. 1-13. ISSN 1610-2940 E-ISSN 0948-5023

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Abstract

Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites. Docking simulations revealed that ligand A18 has the lowest energy binding (ΔGbind) value of −8.30 kcal mol-1, comparable to OTV with ΔGbind of −8.72 kcal mol-1. A18 formed seven hydrogen bonds (H-bonds) at residues Arg292, Arg371, Asp151, Trp178, Glu227, and Tyr406, while eight H-bonds were formed by OTV with amino acids Arg118, Arg292, Arg371, Glu119, Asp151, and Arg152. Molecular dynamics (MD) simulation was conducted to compare the stability between ligand A18 and OTV with NA. Our simulation study showed that the A18-NA complex is as stable as the OTV-NA complex during the MD simulation of 50 ns through the analysis of RMSD, RMSF, total energy, hydrogen bonding, and MM/PBSA free energy calculations.

Item Type:	Article (Journal)
Additional Information:	7089/63210
Uncontrolled Keywords:	Influenza neuraminidase, Molecular docking, Carvone, MM/PBSA
Subjects:	Q Science > Q Science (General) Q Science > QD Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science Kulliyyah of Science > Department of Biotechnology Kulliyyah of Science > Department of Chemistry
Depositing User:	Dr Shafida Abd Hamid
Date Deposited:	16 Apr 2018 08:59
Last Modified:	19 Oct 2018 09:26
URI:	http://irep.iium.edu.my/id/eprint/63210

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