Understanding COVID-19 infection and possible mutations

Date:
December 8, 2020
Source:
Penn State
Summary:
The binding of a SARS-CoV-2 virus surface protein spike -- a
projection from the spherical virus particle -- to the human cell
surface protein ACE2 is the first step to infection that may lead
to COVID-19 disease.

Researchers computationally assessed how changes to the virus spike
makeup can affect binding with ACE2 and compared results to those
of the original SARS-CoV virus (SARS).



FULL STORY ==========================================================================
The binding of a SARS-CoV-2 virus surface protein spike -- a projection
from the spherical virus particle -- to the human cell surface
protein ACE2 is the first step to infection that may lead to COVID-19
disease. Penn State researchers computationally assessed how changes to
the virus spike makeup can affect binding with ACE2 and compared results
to those of the original SARS-CoV virus (SARS).


==========================================================================
The researchers' original manuscript preprint, made available online in
March, was among the first to computationally investigate SARS-CoV-2's
high affinity, or tendency to bind, with human ACE2. The paper was
published online on Sept.

18 in the Computational and Structural Biotechnology Journal. The work
was conceived and led 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, doctoral student in chemical engineering and co-author
on the paper.

"We wanted to first discern key structural changes that give COVID-19
a higher affinity towards human ACE2 proteins when compared with SARS,
and then assess its potential affinity to livestock or other animal
ACE2 proteins." The researchers computationally modeled the attachment
of SARS-CoV-2 protein spike to ACE2, which is located in the upper
respiratory tract and serves as the entry point for other coronaviruses, including SARS. The team used a molecular modeling approach to compute
the binding strength and interactions of the viral protein's attachment
to ACE2.

The team found that the SARS-CoV-2 spike protein is highly optimized to
bind with human ACE2. Simulations of viral attachment to homologous ACE2 proteins of bats, cattle, chickens, horses, felines and canines showed the highest affinity for bats and human ACE2, with lower values of affinity
for cats, horses, dogs, cattle and chickens, according to Chowdhury.

"Beyond explaining the molecular mechanism of binding with ACE2, we
also explored changes in the virus spike that could change its affinity
with human ACE2," said Chowdhury, who earned his doctorate in chemical engineering at Penn State in fall 2019.

Understanding the binding behavior of the virus spike with ACE2 and the
virus tolerance of these structural spike changes could inform future
research on vaccine durability 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 arise 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 may be edited for style and length.


========================================================================== Journal Reference:
1. Ratul Chowdhury, Veda Sheersh Boorla, Costas
D. Maranas. Computational
biophysical characterization of the SARS-CoV-2 spike
protein binding with the ACE2 receptor and implications for
infectivity. Computational and Structural Biotechnology Journal,
2020; 18: 2573 DOI: 10.1016/ j.csbj.2020.09.019 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/12/201208163007.htm

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