To infect our cells, SARS-CoV-2’s spike protein turns the key on the molecular doorway formed by our ACE2 protein. Mutations that adapted its spike protein to human ACE2 helped the virus make its way out of bats, where SARS-related coronaviruses have circulated for thousands of years, and eventually trigger the COVID-19 pandemic. After the smaller SARS epidemic in the early 2000s, COVID-19 is the second viral outbreak driven by a coronavirus that acquired the key to our cells.
New work, published Thursday in the journal Nature from scientists at Fred Hutchinson Cancer Research Center and the University of Washington, suggests that to safeguard against other coronaviruses that could gain the ability to sneak into our cells, we need to think globally. The researchers found that the ability to bind ACE2 — a crucial trait in species-jumping coronaviruses — could be a more widespread possibility than previously thought. Instead of being a late evolutionary development, the ability to bind ACE2 is an ancient property of bat SARS-related coronaviruses — and found in coronaviruses outside of Asia.
The researchers found that many of the coronaviruses that already bind one species’ ACE2 can jump to another species’ ACE2 (including humans’) by switching a single protein building block, or amino acid. Binding to human ACE2 is not the only requirement for spillover into humans, but it’s an important hurdle a coronavirus must clear to start a pandemic, said Dr. Tyler Starr, the postdoctoral fellow in Hutch evolutionary biologist Dr. Jesse Bloom’s lab who led the work.
Researchers who are working on broad coronavirus vaccines and treatments in preparation for future viral spillovers must take these more distantly related viruses into account, he said.
“People who are working on surveillance and therapeutic antibody development need to expand their breadth,” Starr said. “If you don’t test viruses [from around the world] you’re missing the plot. We don’t know where the next pandemic might come from.”
The findings also highlight the care that should be taken in handling and sampling coronaviruses with unknown ACE2 binding potential, he said.
