Research exposes new vulnerability for SARS-CoV-2 8/12/20, 4:26 AM

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AUGUST 11, 2020

Research exposes
new vulnerability for
SARS-CoV-2
by Northwestern University

Computer model showing poly basic cleavage

sites on the novel coronavirus' spike protein.
Credit: Northwestern University.

Northwestern University researchers

have uncovered a new vulnerability in

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the novel coronavirus' infamous spike

protein—illuminating a relatively simple,
potential treatment pathway.

The spike protein contains the virus'

binding site, which adheres to host cells
and enables the virus to enter and
infect the body. Using nanometer-level
simulations, the researchers discovered
a positively charged site (known as the
polybasic cleavage site) located 10
nanometers from the actual binding site
on the spike protein. The positively
charged site allows strong bonding
between the virus protein and the
negatively charged human-cell
receptors.

Leveraging this discovery, the

researchers designed a negatively
charged molecule to bind to the
positively charged cleavage site.
Blocking this site inhibits the virus from
bonding to the host cell.

"Our work indicates that blocking this

cleavage site may act as a viable
prophylactic treatment that decreases
the virus' ability to infect humans," said
Northwestern's Monica Olvera de la

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Cruz, who led the work. "Our results

explain experimental studies showing
that mutations of the SARS-CoV-2
spike protein affected the virus
transmissibility."

The research was published online last

week in the journal ACS Nano.

Olvera de la Cruz is the Lawyer Taylor

Professor of Materials Science and
Engineering in Northwestern's
McCormick School of Engineering.
Baofu Qiao, a research assistant
professor in Olvera de la Cruz's
research group, is the paper's first
author.

Made up of amino acids, SARS-CoV-2's

polybasic cleavage sites have remained
elusive since the COVID-19 outbreak
began. But previous research indicates
that these mysterious sites are
essential for virulence and
transmission. Olvera de la Cruz and
Qiao discovered that polybasic
cleavage site is located 10 nanometers
from human cell receptors—a finding
that provided unexpected insight.

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"We didn't expect to see electrostatic

interactions at 10 nanometers," Qiao
said. "In physiological conditions, all
electrostatic interactions no longer
occur at distances longer than 1
nanometer."

"The function of the polybasic cleavage

site has remained elusive," Olvera de la
Cruz said. "However, it appears to be
cleaved by an enzyme (furin) that is
abundant in lungs, which suggests the
cleavage site is crucial for virus entry
into human cells."

With this new information, Olvera de la

Cruz and Qiao next plan to work with
Northwestern chemists and
pharmacologists to design a new drug
that could bind to the spike protein.

More information: Baofu Qiao et al,

Enhanced Binding of SARS-CoV-2 Spike
Protein to Receptor by Distal Polybasic
Cleavage Sites, ACS Nano (2020). DOI:
10.1021/acsnano.0c04798

Journal information: ACS Nano

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Provided by Northwestern University

Citation: Research exposes new

vulnerability for SARS-CoV-2 (2020,
August 11) retrieved 12 August 2020
from https://phys.org/news/2020-08-
exposes-vulnerability-sars-cov-.html

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