Source of Oseltamivir Resistance Due to R152K Mutation of Influenza B Virus Neuraminidase: Molecular Modeling
Every 2-3 years the influenza B virus serves
epidemics. Neuraminidase (NA) is an important target for influenza
drug design. Although, oseltamivir, an oral neuraminidase drug, has
been shown good inhibitory efficiency against wild-type of influenza
B virus, the lower susceptibility to the R152K mutation has been
reported. Better understanding of oseltamivir efficiency and
resistance toward the influenza B NA wild-type and R152K mutant,
respectively, could be useful for rational drug design. Here, two
complex systems of wild-type and R152K NAs with oseltamivir
bound were studied using molecular dynamics (MD) simulations.
Based on 5-ns MD simulation, the loss of notable hydrogen bond and
decrease in per-residue decomposition energy from the mutated
residue K152 contributed to drug compared to those of R152 in wildtype
were found to be a primary source of high-level of oseltamivir
resistance due to the R152K mutation.
[1] World Health Organization. Influenza web page [accessed on 3
September 2010]. http://www.who.int/mediacentre/factsheets/fs211/en/
[2] D. Jackson, R. A. Elderfield, and W. S. Barclay, "Molecular studies of
influenza B virus in the reverse genetics era," Journal of General
Virology, vol. 92, pp. 1-17, 2011.
[3] L. V. Gubareva, L. Kaiser, and F. G. Hayden, "Influenza virus
neuraminidase inhibitors," Lancet, vol. 355, pp. 827-35, 2000.
[4] B. K. Kamps, C. Hoffmann, and W. Presier, Influenza Report 2006.
Frying Publisher, Paris, 2006, pp. 87-91.
[5] S. J. Gamblin, and J. J. Skehel, "Influenza hemagglutinin and
neuraminidase membrane glycoproteins," Journal of Biological
Chemistry, vol. 285, pp. 28403-409, 2010.
[6] N. Suguya, K. Mitamura, M. Yamazaki, D. Tamura, M. Ichikawa, and
K. Kimura, et al., "Lower clinical effectiveness of oseltamivir against
influenza B constasted with influenza A infection in children," Clinical
Infectious Diseases, vol. 44, pp. 197-202, 2007.
[7] V. P. Mishin, F. G. Hayden, and L.V. Gubareva, "Susceptibilities of
antiviral-resistant influenza viruses to novel neuraminidase inhibitors,"
Antimicrobial Agents and Chemotherapy, vol. 49, pp. 4515-520, 2005.
[8] D. Jackson, W. Barclay, and T. ZÜrcher, "Characterization of
recombinant influenza B viruses with key neuraminidase inhibitor
resistance mutations," Journal of Antimicrobial Chemotherapy, vol. 55,
pp. 162-69, 2005.
[9] T. G. Sheu, V. M. Deydel, R. J. Garten, A. I. Klimov, and L. V.
Gubareva "Detection of antiviral resistance and genetic lineage
markers in influenza B virus neuraminidase using pyrosequencing,"
Antiviral Research, vol. 85, pp. 354-60, 2010.
[10] O. Ferraris, and B. Lina, "Mutations of neuraminidase implicated in
neuraminidase inhibitors resistance," Journal of Clinical Virology, vol.
41, pp. 13-19, 2008.
[11] W. P. Burmeister, B. Henrissat, C. Bosso, S. Cusack, and R. W.
Ruigrok, " Influenza B virus neuraminidase can synthesize its own
inhibitor," Structure, vol. 1, pp. 19-26, 1993.
[12] M. N. Janakiraman, C. L. White, W. G. Laver, G. M. Air, and M. Luo, "
Structure of influenza virus neuraminidase B/Lee/40 complexed with
sialic acid and a dehydro analog at 1.8-Å resolution: Implications for the
catalytic mechanism7," Biochemistry, vol. 33, pp. 8172-79, 1994.
[13] A. J. Oakley, S. Barrett, T.S. Peat, J. Newman, V. A. Streltsov, L.
Waddington, et al., "Structural and Functional Basis of Resistance to
Neuraminidase Inhibitors of Influenza B Viruses," Journal of Medical
Chemistry, vol. 53, pp. 6421-31, 2010.
[14] D. C. Bas, D. M. Rogers, and J. H. Jensen, " Very fast prediction and
rationalization of pKa values for protein-ligand complexes," Proteinsl,
vol.73, pp. 765-83, 2008.
[15] D. A. Case, T. A. Darden, T. E. Cheatham III, C. L. Simmerling, J.
Wang, R. E. Duke, et al., AMBER 10, University of California ,San
Francisco, 2008.
[16] W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, R. W. Impey, and M.
L. Klein, " Comparison of simple potential functions for simulating
liquid water," The Journal pf Chemicla Physics, vol.79, pp. 926-35,
1983.
[17] T. Darden, D. York, and L. Pedersen, " Particle mesh Ewald an Nlog(
N) method for Ewald sums in large systems," Journal of Chemical
Physics, vol. 98, pp. 10089-92, 1993.
[1] World Health Organization. Influenza web page [accessed on 3
September 2010]. http://www.who.int/mediacentre/factsheets/fs211/en/
[2] D. Jackson, R. A. Elderfield, and W. S. Barclay, "Molecular studies of
influenza B virus in the reverse genetics era," Journal of General
Virology, vol. 92, pp. 1-17, 2011.
[3] L. V. Gubareva, L. Kaiser, and F. G. Hayden, "Influenza virus
neuraminidase inhibitors," Lancet, vol. 355, pp. 827-35, 2000.
[4] B. K. Kamps, C. Hoffmann, and W. Presier, Influenza Report 2006.
Frying Publisher, Paris, 2006, pp. 87-91.
[5] S. J. Gamblin, and J. J. Skehel, "Influenza hemagglutinin and
neuraminidase membrane glycoproteins," Journal of Biological
Chemistry, vol. 285, pp. 28403-409, 2010.
[6] N. Suguya, K. Mitamura, M. Yamazaki, D. Tamura, M. Ichikawa, and
K. Kimura, et al., "Lower clinical effectiveness of oseltamivir against
influenza B constasted with influenza A infection in children," Clinical
Infectious Diseases, vol. 44, pp. 197-202, 2007.
[7] V. P. Mishin, F. G. Hayden, and L.V. Gubareva, "Susceptibilities of
antiviral-resistant influenza viruses to novel neuraminidase inhibitors,"
Antimicrobial Agents and Chemotherapy, vol. 49, pp. 4515-520, 2005.
[8] D. Jackson, W. Barclay, and T. ZÜrcher, "Characterization of
recombinant influenza B viruses with key neuraminidase inhibitor
resistance mutations," Journal of Antimicrobial Chemotherapy, vol. 55,
pp. 162-69, 2005.
[9] T. G. Sheu, V. M. Deydel, R. J. Garten, A. I. Klimov, and L. V.
Gubareva "Detection of antiviral resistance and genetic lineage
markers in influenza B virus neuraminidase using pyrosequencing,"
Antiviral Research, vol. 85, pp. 354-60, 2010.
[10] O. Ferraris, and B. Lina, "Mutations of neuraminidase implicated in
neuraminidase inhibitors resistance," Journal of Clinical Virology, vol.
41, pp. 13-19, 2008.
[11] W. P. Burmeister, B. Henrissat, C. Bosso, S. Cusack, and R. W.
Ruigrok, " Influenza B virus neuraminidase can synthesize its own
inhibitor," Structure, vol. 1, pp. 19-26, 1993.
[12] M. N. Janakiraman, C. L. White, W. G. Laver, G. M. Air, and M. Luo, "
Structure of influenza virus neuraminidase B/Lee/40 complexed with
sialic acid and a dehydro analog at 1.8-Å resolution: Implications for the
catalytic mechanism7," Biochemistry, vol. 33, pp. 8172-79, 1994.
[13] A. J. Oakley, S. Barrett, T.S. Peat, J. Newman, V. A. Streltsov, L.
Waddington, et al., "Structural and Functional Basis of Resistance to
Neuraminidase Inhibitors of Influenza B Viruses," Journal of Medical
Chemistry, vol. 53, pp. 6421-31, 2010.
[14] D. C. Bas, D. M. Rogers, and J. H. Jensen, " Very fast prediction and
rationalization of pKa values for protein-ligand complexes," Proteinsl,
vol.73, pp. 765-83, 2008.
[15] D. A. Case, T. A. Darden, T. E. Cheatham III, C. L. Simmerling, J.
Wang, R. E. Duke, et al., AMBER 10, University of California ,San
Francisco, 2008.
[16] W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, R. W. Impey, and M.
L. Klein, " Comparison of simple potential functions for simulating
liquid water," The Journal pf Chemicla Physics, vol.79, pp. 926-35,
1983.
[17] T. Darden, D. York, and L. Pedersen, " Particle mesh Ewald an Nlog(
N) method for Ewald sums in large systems," Journal of Chemical
Physics, vol. 98, pp. 10089-92, 1993.
@article{"International Journal of Biological, Life and Agricultural Sciences:54548", author = "J. Tengrang and T. Rungrotmongkol and S. Hannongbua", title = "Source of Oseltamivir Resistance Due to R152K Mutation of Influenza B Virus Neuraminidase: Molecular Modeling", abstract = "Every 2-3 years the influenza B virus serves
epidemics. Neuraminidase (NA) is an important target for influenza
drug design. Although, oseltamivir, an oral neuraminidase drug, has
been shown good inhibitory efficiency against wild-type of influenza
B virus, the lower susceptibility to the R152K mutation has been
reported. Better understanding of oseltamivir efficiency and
resistance toward the influenza B NA wild-type and R152K mutant,
respectively, could be useful for rational drug design. Here, two
complex systems of wild-type and R152K NAs with oseltamivir
bound were studied using molecular dynamics (MD) simulations.
Based on 5-ns MD simulation, the loss of notable hydrogen bond and
decrease in per-residue decomposition energy from the mutated
residue K152 contributed to drug compared to those of R152 in wildtype
were found to be a primary source of high-level of oseltamivir
resistance due to the R152K mutation.", keywords = "Influenza B neuraminidase, Molecular dynamics
simulation, Oseltamivir resistance, R152K mutant", volume = "6", number = "6", pages = "340-4", }
