Oxford Scientists Simulate Influenza Virus on a Computer

In order to find the weak points of growth and transmission of the influenza virus, researchers at University of Oxford have created a highly accurate computer simulation of the outer shell of the influenza A virion derived using different imaging modalities.

The team brought together data gathered using X-ray crystallography, NMR spectroscopy, cryoelectron microscopy, and lipidomics into what’s called a “coarse-grained molecular dynamics simulation.” This technique allows the model virus to be put through different virtual environments, each having varying temperatures and lipid compositions. The current simulations are still quite limited, but the technique should lead to more complicated tests involving potential therapies and different chemical agents.

The findings of the study are being presented this week at the Biophysical Society’s 59th annual meeting in Baltimore, Maryland.

From the announcement:

Their computer simulation begins by rendering the virus as a relatively large, 73-nanometer ball of loosely packed lipids. This ball then relaxes down into a smaller, 59-nanometer virion within 300 nanoseconds – an imperceptible amount of time on the macroscopic level, but roughly 1/15th of the simulation’s total run time. The viral spike proteins are then embedded into the lipid envelope individually, before adding solvent to the system.

From the simulation, Reddy and coworkers have found that the viral spike proteins protruding from the virion’s membrane spread out, rather than aggregating close together. This is key to the strength of the interactions between influenza A virions and host cells, which are determined by the number of spike proteins that can engage with receptors.

The researchers also observed that the Forssman glycolipid had a role in preventing protein aggregation and slowing down protein diffusion. Reddy indicated it would be important to include glycolipids in future virion simulations given their influence on the biophysical properties observed. The extended sugar head groups of glycolipids may also mask antibody accessibility of the M2 proton channels in the flu envelope — the target of commonly prescribed anti-influenza drugs based on adamantane derivatives.

Biophysical Society: “Virtual Virus” Unfolds the Flu on a CPU…