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Binding of a SARS-CoV-2 virus surface protein spike, a projection of the spherical virus particle, to the human cell surface protein ACE2 is the first step towards infection that can lead to disease COVID-19. The Penn State researchers computationally evaluated how changes in the composition of the virus peak may affect ACE2 binding and compared the results with those of the original SARS-CoV virus (SARS).
The preprint of the researchers’ original manuscript, available online in March, was one of the first to computationally investigate the high affinity or tendency to bind of SARS-CoV-2 with human ACE2. The document was published online on September 18 at the Journal of Computational and Structural Biotechnology. The work was conceived and directed by Costas Maranas, Donald B. Broughton Professor in the Department of Chemical Engineering, and his former graduate student Ratul Chowdhury, who is currently a postdoctoral fellow at Harvard Medical School.
“We were interested in answering two important questions,” said Veda Sheersh Boorla, a doctoral student in chemical engineering and a co-author of the paper. “We wanted to first discern the key structural changes that give COVID-19 a higher affinity for human ACE2 proteins compared to SARS, and then assess its potential affinity for livestock or other animal ACE2 proteins.”
The researchers computationally modeled the binding of the SARS-CoV-2 protein spike to ACE2, which is found in the upper respiratory tract and serves as an entry point for other coronaviruses, including SARS. The team used a molecular modeling approach to calculate the binding strength and interactions of the viral protein’s binding to ACE2.
The team discovered that the SARS-CoV-2 spike protein is highly optimized to bind with human ACE2. Simulations of viral binding to homologous ACE2 proteins from bats, cattle, chickens, horses, felines and canines showed the highest affinity for bats and human ACE2, with the lowest affinity values for cats, horses, dogs, cattle and chickens. , according to Chowdhury.
“Beyond explaining the molecular mechanism of binding to ACE2, we also explored changes in the peak of the virus that could change its affinity for human ACE2,” said Chowdhury, who earned his Ph.D. in chemical engineering from Penn State in the fall of 2019.
Understanding the binding behavior of the virus peak with ACE2 and the virus’s tolerance to these structural peak changes could inform future research on the durability of the vaccine and the potential for the virus to spread to other species.
“The computational workflow that we have established should be able to handle other receptor binding mediated entry mechanisms for other viruses that may emerge in the future,” Chowdhury said.
The Department of Agriculture, the Department of Energy, and the National Science Foundation supported this work.
Story Source:
Materials provided by Penn State. Original written by Gabrielle Stewart. Note: content can be edited for style and length.
