Exploring the cause of oseltamivir resistance against mutant H274Y neuraminidase by molecular simulation approach.

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.

authors

Karthick V,Shanthi V,Rajasekaran R,Ramanathan K

doi

10.1007/s12010-012-9687-7

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

237-49

issue

2

eissn

0273-2289

issn

1559-0291

journal_volume

167

pub_type

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