In a just published paper in Nature Biotechnology, scientists here at the Institute for Protein Design at the University of Washington went a step further and demonstrated a new way to shut down the flu: They used computer modeling to build a completely new kind of antiviral protein with three sticky hands.
Why three? It turns out many deadly envelope viruses – like influenza, Ebola and HIV – build their spike proteins out of three symmetric parts.
A single antiviral drug with three properly spaced hands should be able to symmetrically grab each part of a spike protein, leading to tighter binding and overall better antiviral activity. This geometric feat is beyond what the human immune system can naturally do.
Left: The tips of many viral spike proteins are built out of three symmetric parts, with one part highlighted in pink. Right: A new three-handed antiflu protein (blue) bound to influenza’s HA spike. UW Institute for Protein Design, CC BY-ND
The design strategy worked. The best three-handed protein, called Tri-HSB.1C, was able to bind tightly to diverse strains of influenza. When given to mice, it also afforded complete protection against a lethal flu infection with only minimal associated weight loss – a trait commonly used to diagnose flu severity in mice. Researchers are now applying the same tools to the Ebola spike protein.
It will be many years before this new technology is approved for use in humans, for any virus. But we may not have to wait long to see some lifesaving benefits.