UC San Diego researchers find coronavirus ‘gates’ that allow infection

COVID-19 image

A team led by researchers at UC San Diego says it has discovered how glycans — molecules that make up a sugary residue around the edges of the spike protein — act as infection gateways for SARS-CoV-2, the coronavirus that causes COVID-19, which may be a key to countering the virus.

Since the early days of the COVID pandemic, scientists have pursued the secrets of the mechanisms that allow the virus to enter and infect healthy human cells.

Early in the pandemic, UCSD’s Rommie Amaro, a computational biophysical chemist, helped develop a detailed visualization of the SARS-CoV-2 spike protein that efficiently latches onto human cell receptors.

A study published Aug. 19 in the journal Nature Chemistry, led by Amaro, Lillian Chong of the University of Pittsburgh, UCSD graduate student Terra Sztain and UCSD postdoctoral scholar Surl-Hee Ahn, describes the discovery of glycan “gates” that open to allow the coronavirus’s entry.

“We essentially figured out how the spike actually opens and infects,” said Amaro, a senior author of the study. “We’ve unlocked an important secret of the spike in how it infects cells. Without this gate, the virus basically is rendered incapable of infection.”

Amaro said she believes the research team’s gate discovery opens potential avenues for new therapeutics to counter SARS-CoV-2 infection. If glycan gates could be pharmacologically “locked” in the closed position, the virus effectively would be prevented from entering.

The spike’s coating of glycans helps deceive the human immune system since it comes across as nothing more than a sugary residue. Previous technologies that imaged the structures depicted glycans in static open or closed positions, which initially didn’t draw much interest from scientists.

Supercomputing simulations enabled the researchers to develop dynamic “movies” that revealed glycan gates activating from one position to another, offering an unprecedented piece of the infection story.

“We were actually able to watch the opening and closing,” Amaro said. “That’s one of the really cool things these simulations give you — the ability to see really detailed movies.

“When you watch them, you realize you’re seeing something that we otherwise would have ignored. You look at just the closed structure, and then you look at the open structure, and it doesn’t look like anything special. It’s only because we captured the movie of the whole process that you actually see it doing its thing.” ◆