Neuropilin-1 drives SARS-CoV-2 infectivity, finds breakthrough study
Findings reveal potential anti-viral treatment by targeting how virus
hijacks cells

Date:
October 20, 2020
Source:
University of Bristol
Summary:
Researchers have potentially identified what makes SARS-CoV-2
highly infectious and able to spread rapidly in human cells. The
findings describe how the virus's ability to infect human cells
can be reduced by inhibitors that block a newly discovered
interaction between virus and host, demonstrating a potential
anti-viral treatment.



FULL STORY ==========================================================================
In a major breakthrough an international team of scientists, led by the University of Bristol, has potentially identified what makes SARS-CoV-2
highly infectious and able to spread rapidly in human cells. The findings, published in Science today [20 October] describe how the virus's ability
to infect human cells can be reduced by inhibitors that block a newly discovered interaction between virus and host, demonstrating a potential anti-viral treatment.


========================================================================== Unlike other coronavirus, which cause common colds and mild respiratory symptoms, SARS-CoV-2, the causative agent of COVID-19, is highly infective
and transmissive. Until now, major questions have remained unanswered
as to why SARS-CoV-2 readily infects organs outside of the respiratory
system, such as the brain and heart.

To infect humans, SARS-CoV-2 must first attach to the surface of human
cells that line the respiratory or intestinal tracts. Once attached, the
virus invades the cell then replicates multiple copies of itself. The replicated viruses are then released leading to the transmission of
SARS-CoV-2.

The virus's process of attachment to and invasion of human cells is
performed by a viral protein, called the 'Spike' protein. Understanding
the process by which the 'Spike' protein recognises human cells is central
to the development of antiviral therapies and vaccines to treat COVID-19.

In this breakthrough study, the research groups in Bristol's Faculty of
Life Sciences, Professor Peter Cullen from the School of Biochemistry;
Dr Yohei Yamauchi, Associate Professor and virologist from the School
of Cellular and Molecular Medicine, and Dr Boris Simonetti, a senior
researcher in the Cullen lab, used multiple approaches to discover that SARS-CoV-2 recognises a protein called neuropilin-1 on the surface of
human cells to facilitate viral infection.

Yohei, Boris and Pete explained: "In looking at the sequence of the
SARS-CoV- 2 Spike protein we were struck by the presence of a small
sequence of amino acids that appeared to mimic a protein sequence found in human proteins which interact with neuropilin-1. This led us to propose
a simple hypothesis: could the Spike protein of SARS-CoV-2 associate
with neuropilin-1 to aid viral infection of human cells? Excitingly,
in applying a range of structural and biochemical approaches we have
been able to establish that the Spike protein of SARS-CoV-2 does indeed
bind to neuropilin-1.

"Once we had established that the Spike protein bound to neuropilin-1
we were able to show that the interaction serves to enhance SARS-CoV-2
invasion of human cells grown in cell culture. Importantly, by using
monoclonal antibodies -- lab-created proteins that resemble naturally
occurring antibodies -- or a selective drug that blocks the interaction we
have been able to reduce SARS- CoV-2's ability to infect human cells. This serves to highlight the potential therapeutic value of our discovery in
the fight against COVID-19." Intriguingly, scientists at the Technical University of Munich, Germany and the University of Helsinki, Finland,
have independently found that neuropilin- 1 facilitates SARS-CoV-2 cell
entry and infectivity.

Together the Bristol researchers concluded: "To defeat COVID-19 we
will be relying on an effective vaccine and an arsenal of anti-viral therapeutics. Our discovery of the binding of the SARS-CoV-2 Spike
to neuropilin-1 and its importance for viral infectivity provides
a previously unrecognised avenue for anti-viral therapies to curb
the current COVID-19 pandemic." The SARS-CoV-2 work at Bristol was
facilitated by Dr Andrew Davidson and Dr David Matthews, Readers in
Virology in the School of Cellular and Molecular Medicine and Bristol
UNCOVER and through key collaborations with Professor Brett Collins of
the University of Queensland, Brisbane, Australia, and Professor Tambet
Teesalu of University of Tartu, Estonia.

The study was funded by grants from the European Research Council,
MRC, Wellcome Trust, Lister Institute of Preventive Medicine, Elizabeth Blackwell Institute, and Swiss National Science Foundation.


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


========================================================================== Journal Reference:
1. James L. Daly, Boris Simonetti, Katja Klein, Kai-En Chen, Maia
Kavanagh
Williamson, Carlos Anto'n-Pla'garo, Deborah K. Shoemark, Lorena
Simo'n- Gracia, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter
Horvath, Richard B. Sessions, Ari Helenius, Julian A. Hiscox, Tambet
Teesalu, David A. Matthews, Andrew D. Davidson, Brett M. Collins,
Peter J. Cullen, Yohei Yamauchi. Neuropilin-1 is a host factor
for SARS-CoV-2 infection.

Science, Oct. 20, 2020; DOI: 10.1126/science.abd3072 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201020105522.htm

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