Cause of Swine Flu Virus' Resistance to Drugs Found

An international team of scientists has found why and how the deadly swine flu was able to resist anti-flu medicines such as Relanza and Tamiflu.

Scientists used graphics processing units (GPUs) - electronic chips most commonly employed in games - to find how the anti-flu drug became ineffective. They used GPS to study the molecular process that took place when the drugs are used to treat the H1N1-2009 strain of influenza - commonly known as swine flu.

H1N1-2009 is a new, highly adaptive virus derived from different gene segments of swine, avian, and human influenza. H1N1-2009 or swine flu, is a respiratory disease caused by the influenza virus, which affects the respiratory system in humans. It results in nasal secretion, cough and decrease in appetite. Within a few months of its appearance in early 2009, the H1N1-2009 strain caused the first flu pandemic of the 21<sup>st century killing thousands of people across the world.

The antiviral drugs Relenza and Tamiflu, which target the neuraminidase (NA) enzyme, successfully treated the infection but widespread use of the drugs has led to a series of mutations in NA that reduce the drugs' effectiveness.

Clinical study has revealed that the double mutant of swine flu NA known as IRHY2 has reduced the effectiveness of Relenza by 21 times and Tamiflu by 12,374 times and these powerful drugs have become ineffective in treating swine flu.

To know why the drugs have lost their effectiveness on swine flu, scientists had performed long-timescale molecular dynamics (MD) simulations using GPUs. They found that the Tamiflu drug had very few hydrogen bonds between the drugs and the residues in a part of the NA's structure known as the "150-loop".

"Our simulations showed that IRHY became resistant to Tamiflu due to the loss of key hydrogen bonds between the drug and residues in a part of the NA's structure known as the 150-loop," said Professor Adrian Mulholland, scientist at the University of Bristol, in a statement.

"This allowed NA to change from a closed to an open conformation. Tamiflu binds weakly with the open conformation due to poor electrostatic interactions between the drug and the active site, thus rendering the drug ineffective," he added.

Scientists claim that by just increasing hydrogen bonds in the drugs, the drugs will become quite powerful and effective.

"These findings suggest that drug resistance could be overcome by increasing hydrogen bond interactions between NA inhibitors and residues in the 150-loop, with the aim of maintaining the closed conformation," Mulholland said.

Scientists believe that the new study will provide fresh insight that could lead to the development of the next generation of antiviral treatments for flu.