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Recently discovered interaction between virus and cells may explain COVID-19’s high rate of infection



How SARS-CoV-2 Spike S protein binds to human ACE2 receptor

The S protein has a very flexible stem that consists of two independent joints. The flexible motions of the S-proteins allow the receptor binding domain to have different orientations, and the most likely S-protein configurations are competent for ACE2 binding. Credit: Dr. Yeolkyo Choi

Lehigh researchers quantify the specific interaction between the spike protein from SARS-CoV-2 the virus that causes COVID-19 – with ACE2 receptors in human cells, which may partly explain its high rate of infection compared to SARS-CoV-1.

Bioengineering researchers know Lehigh University has identified a previously unknown interaction between receptors in human cells and the tip, or “S”, protein of SARS-CoV-2, the virus that causes COVID-19. This new information may help in the development of new strategies to block SARS-CoV-2 penetration into human cells.

X. Frank Zhang and Wonpil Im knew from recent studies that the interaction between the SARS-CoV-2 peak protein and angiotensin-converting enzyme 2 (ACE2) receptors in human cells is stronger than the interaction between the structurally identical spike protein from SARS-CoV-1, the virus that caused the SARS outbreak in 2002-2004 and the same receptors.

“Our goal was to characterize SARS-CoV-2 and study protein-protein interactions during its invasion of human cells to provide more insight into the mechanisms that make this first step in its successful invasion process possible,” said Zhang, associate professor of biotechnology and mechanical engineering and mechanics at Lehigh.

Their findings appear in an article entitled “Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction” in a special issue of Biophysical journal, “Biophysicists Address Covid-19 Challenges I,” published in mid-March. Additional authors include from Lehigh University: Wenpeng Cao, Decheng Hou and Seonghan Kim in Biotechnology; Chuqiao Dong in mechanical engineering and mechanics; and from Lindsley F. Kimball Research Institute, New York Blood Center, Wanbo Tai and Lanying Du.

Using combined single-molecule power spectroscopy and molecular dynamics simulations, Zhang’s and Im’s teams were able to identify a previously unknown interaction between ACE2 glycans (sugar groups attached to the surface of proteins) and the SARS-CoV-2 peak. It is this interaction that seems to be responsible for strengthening the virus-cell interaction. This may partly explain the higher infection rate on COVID-19 compared to the similar virus that caused the SARS outbreak in 2002-2004, they say.

“We were surprised to find that the specific interaction between ACE2 glycans and the SARS-CoV-2 peak protein is what makes the separation of the virus from cells so difficult,” says Im, a professor of biotechnology. , Computer Science, Chemistry and Biological Sciences, as well as the President’s Gifted President of Health, Science and Technology at Lehigh.

To achieve these results, the team used Zhang’s innovative single-molecule detection technology that measures the release force of peak protein-ACE2 receptor interaction. Use ofatom molecular dynamic simulations of the complex system available in the CHARMM GUI developed by Im, they then identified the detailed structural information in this interaction.

“After carefully removing all ACE2 glycans and measuring the force of the interaction, we saw that the potency of the SARS-CoV-2 spike-ACE2 interaction dropped back to levels similar to SARS-CoV-1,” says Zhang.

“It is possible that this newly discovered interaction with ACE2 glycans may be a contributing factor to the higher rates of COVID-19 than the structurally similar SARS-CoV-1, which has a weaker interaction,” says Zhang. “Our hope is that researchers may be able to use this information to develop new strategies to identify, prevent, treat and vaccinate against COVID-19.”

Reference: “Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction” by Wenpeng Cao, Chuqiao Dong, Seonghan Kim, Decheng Hou, Wanbo Tai, Lanying Du, Wonpil Im and X. Frank Zhang, 17. February 2021, Biophysical journal.
DOI: 10.1016 / j.bpj.2021.02.007




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