Structural analysis of COVID-19 spike protein provides insight into its evolution

Date:
July 9, 2020
Source:
The Francis Crick Institute
Summary:
Researchers have characterized the structure of the SARS-CoV-2
spike protein as well as its most similar relative in a bat
coronavirus. The structures provide clues about how the spike
evolved and could help inform vaccine design.



FULL STORY ========================================================================== Researchers at the Francis Crick Institute have characterised the
structure of the SARS-CoV-2 spike protein as well as its most similar
relative in a bat coronavirus. The structures provide clues about how
the spike evolved and could help inform vaccine design.


==========================================================================
A characterising feature of SARS-CoV-2, the virus that causes COVID-19,
is the protein spikes which cover the surface, which the virus uses to
bind with and enter human cells.

Analysing the structure of these spikes could provide clues about the
virus' evolution. It is not yet known how SARS-CoV-2 evolved to infect
humans and whether this happened directly from coronaviruses in bats or
via an intermediary species.

In their study, published in Nature Structural & Molecular Biology, the researchers characterised the spike protein in high resolution using a technique called cryo-electron microscopy, which allowed them to achieve
a greater level of detail than previously reported structures. They
then compared this structure to the spike protein of a bat coronavirus,
RaTG13, which has the most similar spike to that of SARS-CoV-2.

While the spikes as a whole were over 97% similar, the researchers found
a number of significant differences at the location where SARS-CoV-2
binds with a receptor on human cells, called ACE2, and at the surfaces
that keep the subunits of the spike together.

These differences mean the spike of SARS-CoV-2 is more stable and is
able to bind around 1,000 times more tightly to a human cell than this
bat virus.



========================================================================== Based on their findings, the researchers suggest it is unlikely that a bat virus similar to RaTG13 could infect human cells. This supports the theory
that SARS-CoV-2 is the result of different coronaviruses coming together
and evolving over time, potentially also through several host species.

Antoni Wrobel, co-lead author and postdoctoral training fellow in
the Structural Biology of Disease Processes Laboratory at the Crick,
says: "The spike is the entry key that allows SARS-CoV-2 into human
cells. Changes in the virus' genome, which affect the spike's structure, therefore have potential to make the virus either more or less able to
enter the host's cell." "At some point in the evolution of this virus,
it seems to have picked up changes, like the differences we found,
which made it able to infect humans." Donald Benton, co-lead author
and postdoctoral training fellow in the Structural Biology of Disease
Processes Laboratory at the Crick, says: "The exact process of how
SARS-CoV-2 evolved remains unclear and is something many researchers are
trying to piece together. Our work provides a piece of this puzzle,
as it suggests that the virus did not come straight from the bat
coronaviruses currently known." Steve Gamblin, group leader of the
Structural Biology of Disease Processes Laboratory at the Crick says:
"The world was caught off guard by SARS-CoV-2.

Examining the structure of this virus, and its likely precursor, helps
us understand where it came from, and how it interacts with human cells."
The Crick researchers will continue to study the structure of the virus,
with a view to finding further clues as to its evolutionary path.

The spike protein structures are open-access, so other researchers can
use these in their work and to aid with drug discovery and vaccine design.


========================================================================== Story Source: Materials provided by The_Francis_Crick_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Antoni G. Wrobel, Donald J. Benton, Pengqi Xu, Chloe" Roustan,
Stephen R.

Martin, Peter B. Rosenthal, John J. Skehel, Steven
J. Gamblin. SARS-CoV- 2 and bat RaTG13 spike glycoprotein structures
inform on virus evolution and furin-cleavage effects. Nature
Structural & Molecular Biology, 2020; DOI: 10.1038/s41594-020-0468-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200709105122.htm

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