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In silico study of carvone derivatives as potential neuraminidase inhibitors

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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 (∆Gbind) value of −8.30 kcal mol-1, comparable to OTV with ∆Gbind 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.

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Acknowledgments

SAH thanks Malaysia Ministry of Higher Education (MOHE) for Fundamental Research Grant Scheme (FRGS14-098-0339) and myBrain15 scholarship for NJ.

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Authors and Affiliations

  1. Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, 25200, Bandar Indera Mahkota Kuantan, Pahang, Malaysia

    Noorakmar Jusoh & Shafida Abd Hamid

  2. Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia, 25200, Bandar Indera Mahkota Kuantan, Pahang, Malaysia

    Hasanuddin Zainal, Azzmer Azzar Abdul Hamid, Noraslinda M. Bunnori & Khairul Bariyyah Abd Halim

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  1. Noorakmar Jusoh
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  2. Hasanuddin Zainal
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  3. Azzmer Azzar Abdul Hamid
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  5. Khairul Bariyyah Abd Halim
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Correspondence to Shafida Abd Hamid.

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Jusoh, N., Zainal, H., Abdul Hamid, A. et al. In silico study of carvone derivatives as potential neuraminidase inhibitors. J Mol Model 24, 93 (2018). https://doi.org/10.1007/s00894-018-3619-6

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  • DOI: https://doi.org/10.1007/s00894-018-3619-6

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