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Springerplus. 2013 Mar 18;2(1):115. Print 2013 Dec.
Virtual screening for oseltamivir-resistant a (H5N1) influenza neuraminidase from traditional Chinese medicine database: a combined molecular docking with molecular dynamics approach.
Karthick V, Ramanathan K.
Source
Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014 India.
Abstract
The neuraminidase (NA) of the influenza virus is the target of antiviral drug, oseltamivir. Recently, cases are reported that Influenza virus becoming resistant to oseltamivir, necessitating the development of new long-acting antiviral compounds. Most importantly, H274Y mutation in neuraminidase exhibits high levels of resistance to oseltamivir. In this report, a novel class of lead molecule with potential NA inhibitory activity was found from the traditional Chinese medicine database (TCMD) using virtual screening approach. Initially ADME properties of the lead compounds were analyzed with respect to the Lipinski rule of five. Subsequently, the data reduction was carried out by employing molecular docking study. Final validation was done by means of molecular dynamic simulations. The toxicity profiles for the screened compound were also analyzed. The result indicates that neoglucobrassicin (a compound derived from TCMD) become a promising lead compound and be effective in treating oseltamivir-resistant influenza virus strains.
KEYWORDS:
Molecular docking, Molecular dynamic simulation, Oseltamivir-resistance, Traditional Chinese medicine database (TCMD), Virtual screening
PMID:
23638404
[PubMed]
Virtual screening for oseltamivir-resistant a (H5N1) influenza neuraminidase from traditional Chinese medicine database: a combined molecular docking with molecular dynamics approach.
Karthick V, Ramanathan K.
Source
Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014 India.
Abstract
The neuraminidase (NA) of the influenza virus is the target of antiviral drug, oseltamivir. Recently, cases are reported that Influenza virus becoming resistant to oseltamivir, necessitating the development of new long-acting antiviral compounds. Most importantly, H274Y mutation in neuraminidase exhibits high levels of resistance to oseltamivir. In this report, a novel class of lead molecule with potential NA inhibitory activity was found from the traditional Chinese medicine database (TCMD) using virtual screening approach. Initially ADME properties of the lead compounds were analyzed with respect to the Lipinski rule of five. Subsequently, the data reduction was carried out by employing molecular docking study. Final validation was done by means of molecular dynamic simulations. The toxicity profiles for the screened compound were also analyzed. The result indicates that neoglucobrassicin (a compound derived from TCMD) become a promising lead compound and be effective in treating oseltamivir-resistant influenza virus strains.
KEYWORDS:
Molecular docking, Molecular dynamic simulation, Oseltamivir-resistance, Traditional Chinese medicine database (TCMD), Virtual screening
PMID:
23638404
[PubMed]
