Researchers find clues to new mechanisms for coronavirus infections

A group of bat viruses related to SARS-CoV-2 can also infect human cells but use a different and unknown portal of entry.

While researchers are still looking at how these viruses infect cells, the findings could aid in the development of new vaccines that prevent coronaviruses from causing another pandemic.

Publication in the journal, eBioMedicinea team of researchers from Washington State University used a computational approach based on network science to distinguish a group of coronaviruses that can infect human cells from those that cannot. The researchers then confirmed their lab calculation results, showing that a specific group of viruses can infect both human and bat cells.

“What we’re seeing with these viruses is that they’re able to enter cells through another mechanism or receptor, and that has a lot of implications for how, and if, they might infect us,” said Michael Letko, co-lead author and assistant professor at the Paul Allen School of Global Health.

Interspecies transmission of coronaviruses poses a serious threat to global health. While many coronaviruses have been discovered in wildlife, researchers have been unable to predict which poses the greatest threat to humans and are scrambling to develop vaccines after the viruses spread.

“As we encroach more and more on places where there are human and animal interactions, it is very likely that there will be many viruses that will have to be examined,” said Shira Broschat, professor at the School. of Electrical Engineering and Computer Science, also co-lead author on the paper.

SARS-CoV-2, the virus causing the ongoing pandemic, is one of many related viruses that use its spike protein to infect cells by attaching to a receptor protein called enzyme converting enzyme. angiotensin 2 (ACE2). ACE2 receptors are located in many types of human tissues and cells, including the lungs, heart, blood vessels, kidneys, liver, and gastrointestinal tract. In previous studies, Letko has shown that another group of sarbecoviruses, the family to which SARS CoV-2 belongs, can also infect human cells. How they do this is still a mystery. Sarbecoviruses are present in bats and other mammals worldwide.

The researchers started with a database containing more than 1.6 million sarbecovirus entries. To better understand what distinguishes animal viruses that can infect human cells from those that cannot, the researchers constructed network maps showing the relatedness of viral spike sequences. When the team focused their attention on a small part of the spike protein used by some coronaviruses to bind to receptors, they found that their network map had organized the viruses into clusters that separated those that can infect human cells. and those who cannot.

“So many people sequence genomes because it’s pretty cheap and easy to do, but you have to make sense of all that sequence,” Broschat said. “We need to understand the relationships between the sequences. »

With this tiny region of the spike protein in their sights, the researchers then turned to the lab. Letko’s team specializes in studying how viruses infect cells and were able to demonstrate that this region of the spike protein can actually allow non-infectious virus-like particles to invade cell cultures. human cells. The team’s extensive lab results confirmed the accuracy of the network map.

Researchers still don’t know which receptors are involved and whether this route of infection is actually efficient enough for cross-species spillover to occur, but they have identified a region on virus spikes that appears to be critical for how which group of viruses can infect several different cell types in several different species – information that will be critical for vaccine development.

The researchers hope that as new viruses are discovered in this family of viruses, scientists will be able to examine them at the computational level and make a prediction of what they will do in the lab.

“It’s like a detective story — you hunt and hunt, and you get the story more and more clearly,” Broschat said. “Now okay, who’s the bad guy?” »

The work was funded by WSU and the Paul G. Allen School for Global Health.

Source of the story:

Materials provided by Washington State University. Original written by Tina Hilding. Note: Content may be edited for style and length.

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