The inhibitory performance of flavonoid cyanidin-3-sambubiocide against H274Y mutation in H1N1 influenza virus

Abstract

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 report that 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 150th loop of the MT protein has found more deformation than WT. A single H274Y mutation induces the conformational changes in the 150th loop which leads to produce more resistance to oseltamivir. The 150th cavity is more attractive target for C3S to stop the conformational changes in the MT, than 430th 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.

Keywords:

• Influenza virus
• drug resistance
• H274Y mutation
• molecular docking
• molecular dynamic simulation

Acknowledgment

The authors would like to thank CMSD (Center for Modelling Simulation and Design)-DST, Government of India at Hyderabad for allowing us to use the facility. S. Kannan expresses his sincere thanks to Govt. Of India, CSIR, New Delhi for the award of Senior Research Fellowship (Grant No: 09/472(0177)/2016- EMR-I dated: 31.03.2017). Prof. P. Kolandaivel is thankful to UGC for the award of UGC BSR faculty fellowship.