Abstract
Oseltamivir (Tamiflu) is the preferred anti-viral drug employed to fight the flu virus in infected individuals. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infections. Until recently, only a low prevalence of neuraminidase inhibitors (NAIs) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a H274Y neuraminidase mutation that was highly resistant to the NAI, oseltamivir. In this study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular docking and molecular dynamics simulation approach. Our results suggested that wild-type NA could be more indispensable for the oseltamivir binding, as characterized by minimum number of H-bonds, high flexibility and largest binding affinity than mutant-type NA. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.
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Acknowledgments
The authors express deep sense of gratitude to the management of Vellore Institute of Technology for all the support, assistance, and constant encouragements to carry out this work. The authors also thank Professor M.A. Mohamed Sahul Hameed, English division, for English editing and grammar corrections in our manuscript.
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Karthick, V., Shanthi, V., Rajasekaran, R. et al. Exploring the Cause of Oseltamivir Resistance Against Mutant H274Y Neuraminidase by Molecular Simulation Approach. Appl Biochem Biotechnol 167, 237–249 (2012). https://doi.org/10.1007/s12010-012-9687-7
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DOI: https://doi.org/10.1007/s12010-012-9687-7