tetano
Editor, Senior Moderator
J Biomol Struct Dyn. 2017 Dec 3:1-64. doi: 10.1080/07391102.2017.1413422. [Epub ahead of print]
[h=1]The inhibitory performance of flavonoid cyanidin-3-sambubiocide against H274Y mutation in H1N1 influenza virus.[/h] Kannan S[SUP]1[/SUP], Kolandaivel P[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Oseltamivir (Tamiflu) is the most accepted antiviral drug that targets the neuraminidase (NA) protein to inhibit the viral release from the host cell. Few H1N1 influenza strains with the H274Y mutation creates drug-resistance to oseltamivir. In this study, we reported flavonoid cyanidin-3-sambubiocide (C3S) compound acts as a potential inhibitor against H274Y mutation. The drug-resistance mechanism and inhibitory activity of C3S and oseltamivir against wild type (WT) and H274Y mutant type (MT) have been studied and compared based on the results of molecular docking, molecular dynamics and quantum chemical methods. Oseltamivir has been found less binding affinity with MT. C3S has more binding affinity with WT and MT proteins. From the dynamical study, the 150[SUP]th[/SUP] loop of the MT protein has found more deformation than WT. A single H274Y mutation induces the conformational changes in the 150[SUP]th[/SUP] loop which leads to produce more resistance to oseltamivir. The 150[SUP]th[/SUP] cavity is more attractive target for C3S to stop the conformational changes in the MT, than 430[SUP]th[/SUP] cavity of NA protein. The C3S is stabilized with MT by more number of hydrogen bonds than oseltamivir.The electrostatic interaction energy shows a stronger C3S binding with MT and this compound may be more effective against oseltamivir-resistant virus strains.
[h=4]KEYWORDS:[/h] Drug resistance; H274Y mutation; Influenza virus; Molecular docking; Molecular dynamic simulation
PMID: 29199545 DOI: 10.1080/07391102.2017.1413422
[h=1]The inhibitory performance of flavonoid cyanidin-3-sambubiocide against H274Y mutation in H1N1 influenza virus.[/h] Kannan S[SUP]1[/SUP], Kolandaivel P[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Oseltamivir (Tamiflu) is the most accepted antiviral drug that targets the neuraminidase (NA) protein to inhibit the viral release from the host cell. Few H1N1 influenza strains with the H274Y mutation creates drug-resistance to oseltamivir. In this study, we reported flavonoid cyanidin-3-sambubiocide (C3S) compound acts as a potential inhibitor against H274Y mutation. The drug-resistance mechanism and inhibitory activity of C3S and oseltamivir against wild type (WT) and H274Y mutant type (MT) have been studied and compared based on the results of molecular docking, molecular dynamics and quantum chemical methods. Oseltamivir has been found less binding affinity with MT. C3S has more binding affinity with WT and MT proteins. From the dynamical study, the 150[SUP]th[/SUP] loop of the MT protein has found more deformation than WT. A single H274Y mutation induces the conformational changes in the 150[SUP]th[/SUP] loop which leads to produce more resistance to oseltamivir. The 150[SUP]th[/SUP] cavity is more attractive target for C3S to stop the conformational changes in the MT, than 430[SUP]th[/SUP] cavity of NA protein. The C3S is stabilized with MT by more number of hydrogen bonds than oseltamivir.The electrostatic interaction energy shows a stronger C3S binding with MT and this compound may be more effective against oseltamivir-resistant virus strains.
[h=4]KEYWORDS:[/h] Drug resistance; H274Y mutation; Influenza virus; Molecular docking; Molecular dynamic simulation
PMID: 29199545 DOI: 10.1080/07391102.2017.1413422