Researchers from Rice University identify mechanism of the flu virus infection by an atom-level simulation.
The protein, hemagglutinin, which is located on the surface of flu viruses helps them attach to and transport through the protective membranes of target cells. The researchers developed a mechanism that enables the protein to unfold and refold in a snap. This alters its form that leads to the exposure of a peptide capable of attaching the virus to a cell to start the infection. Therapeutic drugs that target the exposed peptide could shut the virus down and prevent infection. The single conserved amino acid residue in the virus is responsible for pause in the process of refolding the protein. The pause fusion peptide buried inside to bind to the target cell and begin infecting it. Therapies that could restrict the pause could lead to the quick refolding making it difficult for binding to take place.
In microscopic observation it was evident that in the B-loop of the HA2 domain of the protein, HA2 sits beneath another domain— a cap known as HA1—which is capable of mutation to escape past defenses. It defines HA1 as a common target for flu medications as the exposed cap domain is more accessible than the protected HA2 domain. However, HA1 is capable of constant mutation to resist drugs, which leaves HA2 as a promising target for drugs as the domain cannot escape by mutating as mutation would make it nonfunctional. HA2 transforms itself from a random loop to a coiled coil, when triggered by acidic conditions in the environment near a target cell. It eventually unfolds and refolds in a fraction of a second even with a pause. The researchers modeled 40 microseconds of the HA2 domain transition, which takes 1.4 milliseconds to complete. The current research focused strain responsible for the Hong Kong flu and the Spanish flu. The research was published in the Proceedings of the National Academy of Sciences on July 16, 2018.