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Monday, December 05, 2022

Computational network science approach reveals new mechanism for coronavirus infection

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

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

Published in the journal, eBioMedicine, a team of researchers from Washington State University used a computational approach based on network science to differentiate between a group of coronaviruses that can infect human cells from those that cannot. Huh. The researchers then confirmed their computational results in the laboratory, showing that a specific group of viruses can infect both human and bat cells.

What we find with these viruses is that they are able to enter cells through some other mechanism or receptor, and that has a lot of implications for how and if they will be able to infect us.”


Michael Letko, co-senior author and assistant professor, Paul Allen School of Global Health

Cross-species transmission of coronavirus has become a serious threat to global health. While many coronaviruses have been discovered in wildlife, researchers have not been able to predict which ones pose the greatest threat to humans and scrambling to develop vaccines after the virus has spread.

Professor Shira Brosch in the School of Electrical Engineering and Computer Science said, “As we encroach on more and more places where human and animal interactions take place, it is quite likely that there will be many viruses that will need to be investigated. ” Co-senior author on the paper.

SARS-CoV-2, the virus behind the ongoing pandemic, is one of several related viruses that use their spike proteins to infect cells by binding to a receptor protein called angiotensin converting enzyme 2 (ACE2). ACE2 receptors are located in many types of human tissues and cells, including the lungs, heart, blood vessels, kidney, liver, and gastrointestinal tract. In earlier studies, Letko showed that another group of sarbecoviruses, the family to which SARS CoV-2 belongs, can also infect human cells. How they do it is still a mystery. Sarbecoviruses are found worldwide in bats and other mammals.

The researchers started with a database that contained more than 1.6 million cerbecovirus entries. To better understand how animal viruses differ from those that can infect human cells, which cannot, the researchers created network maps showing the relatedness of viral spike sequences. When the team turned their attention to a small part of the spike protein used by some coronaviruses to bind to receptors, they found that their network map organized the viruses into groups that differentiated those Those that could infect human cells and those that could not.

“Many people are sequencing the genome because it’s fairly cheap and easy to do, but you have to understand all of these sequences,” Brochat said. “We need to understand the relationship between the sequences.”

With this much smaller region of the spike protein, the researchers then headed 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 human cell cultures. . The team’s extensive laboratory results confirmed the accuracy of the network map.

Researchers are still unsure which receptors are involved and if this infection pathway is indeed efficient enough for cross-species spillover to occur, but they have identified a region on virus spikes that is important for whether virus groups How can it infect many different people? Types of cells in many different species – information that will be important for vaccine development.

The researchers hope that as new viruses in this virus family are discovered, scientists will be able to observe them at the computational level and predict what they will do in the laboratory.

“It’s like a detective story —; you’re hunting and hunting, and you’re getting the story more and more clearly,” Brochat said. “Now, well, who’s the villain?”

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

Source:

Washington State University

Journal Reference:

Khalidian, E., and others. (2022) Sequence determinants of human cell entry identified in ACE2-independent BAT sarbecovirus: a combined laboratory and computational network science approach. EBiomedicine. doi.org/10.1016/j.ebiom.2022.103990.

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