Computational design of drug candidates for influenza a virus subtype H1N1 by inhibiting the viral neuraminidase-1 enzyme

Usman Sumo Friend Tambunan, Arli Aditya Parikesit, Yonaniko Dephinto, Feimmy Ruth Pratiwi Sipahutar

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

It is critical to seek potential alternative treatments for H1N1 infections by inhibiting neuraminidase-1 enzyme. One of the viable options for inhibiting the activity of neuraminidase-1 is peptide drug design. In order to increase peptide stability, cyclization is necessary to prevent its digestion by protease enzyme. Cyclization of peptide ligands by formation of disulfide bridges is preferable for designing inhibitors of neuraminidase-1 because of their high activity and specificity. Here we designed ligands by using molecular docking, drug scan and dynamics computational methods. Based on our docking results, short polypeptides of cystein-arginine-methionine-tyrosine-proline-cysteine (CRMYPC) and cysteine-arginine-aspargine- phenylalanine-proline-cysteine (CRNFPC) have good residual interactions with the target and the binding energy δGbinding of -31.7402 and -31.0144 kcal mol-1, respectively. These values are much lower than those of the standards, and it means that both ligands are more accessible to ligand-receptor binding. Based on drug scan results, both of these ligands are neither mutagenic nor carcinogenic. They also show good oral bioavailability. Moreover, both ligands show relatively stable molecular dynamics progression of RMSD vs. time plot. However, based on our metods, the CRMYPC ligand has sufficient hydrogen bonding interactions with residues of the active side of neuraminidase-1 and can be therefore proposed as a potential inhibitor of neuraminidase-1.

Original languageEnglish
Pages (from-to)157-172
Number of pages16
JournalActa Pharmaceutica
Volume64
Issue number2
DOIs
Publication statusPublished - Jun 2014

Keywords

  • Cyclic peptide disulfide
  • H1N1
  • Molecular docking
  • Molecular dynamics
  • Neuraminidase-1

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