How Proteins Tilt and ‘Breathe’ on Flu Viruses

The potential “tripledemic” of influenza, SARS-CoV-2 and RSV (respiratory syncytial virus) infection continues to be a concern. Vaccines remain the best defense against COVID-19 and influenza, with the flu vaccine mainly targeting two proteins on the virus’s surface. Now, researchers in ACS Central Science report that simulations show the proteins can tilt and wave in “breath-like” motions, which could be exploited to better defend against the flu.

Source Article

“ Breathing and Tilting: Mesoscale Simulations Illuminate Influenza Glycoprotein Vulnerabilities”
ACS Central Science
Corresponding author: Rommie E. Amaro, Ph.D.,

Transcript

Narrator: With influenza, or “the flu”, COVID-19, and RSV  all circulating at the same time, doctors worry about a “tripledemic.” To develop better flu  vaccines and drugs, researchers reporting in ACS Central Science mapped out the millions of  atoms in an influenza A virion with simulations.

Rommie Amaro’s team studied how the proteins  on the viral particles move and help them infect cells. Their detailed simulations  showed that two proteins on the virus’s surface are quite flexible. First,  as the head on neuraminidase tilts, its underside is accessible to an antibody,  which could attach and neutralize the virus. Second, some hemagglutinins appear to “breathe”  — the top of the protein opens and closes.

In the open state, a different antibody, FluA-20,  can fit into the space. Keeping hemagglutinin open could be exploited to better defend against  the flu virus. Third, both hemagglutinin and neuraminidase can naturally clump together  with up to dozens of nearby proteins. When clustered, the proteins could compete  for the same receptors on host cells, potentially slowing the virus’s entry into or exit  from cells. Ammaro says these visualizations show new vulnerable states of flu viruses, which  could improve future vaccines and treatments.