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Virus-Cell Interaction Explain COVID-19’s High Infection Rate

Researchers quantify the specific interaction between the spike protein of SARS-CoV-2 the Virus that is the root COVID-19’s along with the ACE2 receptors in human cells that may partially explain its high infection rate compared to SARS-CoV-1. Their findings were published in an article called “Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction in a special issue of Biophysical Journal.

The researchers at Lehigh University have found an unknown interaction between receptors in human cells and the spike, or “S,” protein of SARS-CoV-2, the virus that causes COVID-19’s. This information could aid in the development of new strategies to block SARS-CoV-2 entry into human cells.The interaction between the SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 receptors in human cells is stronger than the interaction between the structurally identical spike protein of SARS-CoV-1, the virus that caused the 2002-2004 SARS outbreak, and the same receptors.

Zhang, an associate professor in Bioengineering and Mechanical Engineering & Mechanics at Lehigh said that the goal was to characterize SARS-CoV-2 and study the protein-protein interactions during its invasion of human cells. That provides more insights into the mechanisms that make this preliminary step in its successful invasion process

They used combined single-molecule force spectroscopy and molecular dynamics simulations,  They were able to identify a previously unknown interaction between ACE2 glycans and the SARS-CoV-2 spike. It is this interaction that appears to be responsible for the strengthening of the virus-cell interaction. This may partially explain the higher infection rate of COVID-19’s compared to the similar virus that caused the 2002-2004 SARS outbreak.

The lead author Im and a professor of bioengineering, computer science, chemistry and biological sciences, as well as the Presidential Endowed Chair in Health, Science and Engineering at Lehigh said that the researchers were surprised to find that the specific interaction between ACE2 glycans and the SARS-CoV-2 spike protein is what makes the separation of the virus from cells so difficult.

To arrive at these findings, the team used an innovative single-molecule detection technique, measuring the detachment force of the spike protein-ACE2 receptor interaction. Using the all-atom molecular dynamics simulations of the complex system available in CHARMM-GUI developed by Im, they then identified the detailed structural information in this interaction.

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