According to the World Health Organization, each year there are an estimated 1 billion cases of influenza, between 3-5 million severe cases and up to 650,000 influenza-related respiratory deaths globally. Seasonal flu vaccines must be reformulated each year to match the predominantly circulating strains. When the vaccine matches the predominant strain, it is very effective; however, when it does not match, it may offer little protection.
The main targets of the flu vaccine are two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). While the HA protein helps the virus bind to the host cell, the NA protein acts like scissors to cut the HA away from the cell membrane allowing the virus to replicate.
Although the properties of both glycoproteins have been studied previously, a complete understanding of their movement does not exist.
For the first time, researchers at the University of California San Diego have created an atomic-level computer model of the H1N1 virus that reveals new vulnerabilities through glycoprotein “breathing” and “tilting” movements. This work, published in ACS Central Science, suggests possible strategies for the design of future vaccines and antivirals against influenza.
“When we first saw how dynamic these glycoproteins were, the large degree of breathing and tilting, we actually wondered if there was something wrong with our simulations,” stated Distinguished Professor of Chemistry and Biochemistry Rommie Amaro, who is the principal investigator on the project. “Once we knew our models were correct, we realized the enormous potential this discovery held. This research could be used to develop methods of keeping the protein locked open so that it would be constantly accessible to antibodies.”