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Computer chips of a type more commonly found in games consoles havebeen used by scientists at the University of Bristol to reveal howthe flu virus resists anti-flu drugs such as Relenza and Tamiflu. Professor Adrian Mulholland and Dr Christopher Woods from Bristol'sSchool of Chemistry, together with colleagues in Thailand, usedgraphics processing units (GPUs) to simulate the molecularprocesses that take place when these drugs are used to treat theH1N1-2009 strain of influenza - commonly known as 'swine flu'. Their results, published in Biochemistry, provide new insight thatcould lead to the development of the next generation of antiviraltreatments for flu. H1N1-2009 is a new, highly adaptive virus derived from differentgene segments of swine, avian, and human influenza. Within a fewmonths of its appearance in early 2009, the H1N1-2009 strain causedthe first flu pandemic of the 21st-century. The antiviral drugs Relenza and Tamiflu, which target theneuraminidase (NA) enzyme, successfully treated the infection butwidespread use of these drugs has led to a series of mutations inNA that reduce the drugs' effectiveness. Clinical studies indicate that the double mutant of swine flu NAknown as IRHY2 reduced the effectiveness of Relenza by 21 times andTamiflu by 12,374 times - that is, to the point where it has becomean ineffective treatment. To understand why the effectiveness of Relenza and Tamiflu is soseriously reduced by the occurrence of this mutation, theresearchers performed long-timescale molecular dynamics (MD)simulations using GPUs. Professor Mulholland said: "Our simulations showed that IRHY becameresistant to Tamiflu due to the loss of key hydrogen bonds betweenthe drug and residues in a part of the NA's structure known as the'150-loop'. "This allowed NA to change from a closed to an open conformation.Tamiflu binds weakly with the open conformation due to poorelectrostatic interactions between the drug and the active site,thus rendering the drug ineffective." These findings suggest that drug resistance could be overcome byincreasing hydrogen bond interactions between NA inhibitors andresidues in the 150-loop, with the aim of maintaining the closedconformation. The research was supported by the Engineering and Physical SciencesResearch Council (EPSRC) through a Leadership Fellowship grant toProfessor Mulholland and a software development grant to ProfessorMulholland and Dr Woods. Paper 'Long Time Scale GPU Dynamics Reveal the Mechanism of DrugResistance of the Dual Mutant I223R/H275Y Neuraminidase fromH1N1-2009 Influenza Virus' by Christopher J. Woods, MaturosMalaisree, Naruwan Pattarapongdilok,Pornthep Sompornpisut, SupotHannongbua and Adrian J. Mulholland in Biochemistry. The e-commerce company in China offers quality products such as Joye Ego-T Manufacturer , Mini Electric Cigarette, and more. For more , please visit Mini e Health Cigarette today!
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