Lab-made virus mimics COVID-19 virus
Is safer to work with, can aid efforts to find drugs, vaccines

Date:
July 21, 2020
Source:
Washington University School of Medicine
Summary:
Researchers have created a virus in the lab that infects cells
and interacts with antibodies just like the COVID-19 virus, but
lacks the ability to cause severe disease. This safer virus makes
it possible for scientists who do not have access to high-level
biosafety facilities to join the effort to find drugs or vaccines
for COVID-19.



FULL STORY ========================================================================== [Laboratory researcher, | Credit: (c) tilialucida / stock.adobe.com]
Laboratory researcher, concept photo (stock image).

Credit: (c) tilialucida / stock.adobe.com [Laboratory researcher,
| Credit: (c) tilialucida / stock.adobe.com] Laboratory researcher,
concept photo (stock image).

Credit: (c) tilialucida / stock.adobe.com Close Airborne and potentially deadly, the virus that causes COVID-19 can only be studied safely under high-level biosafety conditions. Scientists handling the infectious
virus must wear full-body biohazard suits with pressurized respirators,
and work inside laboratories with multiple containment levels and
specialized ventilation systems. While necessary to protect laboratory
workers, these safety precautions slow down efforts to find drugs and
vaccines for COVID-19 since many scientists lack access to the required biosafety facilities.


==========================================================================
To help remedy that, researchers at Washington University School of
Medicine in St. Louis have developed a hybrid virus that will enable
more scientists to enter the fight against the pandemic. The researchers genetically modified a mild virus by swapping one of its genes for one
from SARS-CoV-2, the virus that causes COVID-19. The resulting hybrid
virus infects cells and is recognized by antibodies just like SARS-CoV-2,
but can be handled under ordinary laboratory safety conditions.

The study is available online in Cell Host & Microbe.

"I've never had this many requests for a scientific material in such
a short period of time," said co-senior author Sean Whelan, PhD, the
Marvin A.

Brennecke Distinguished Professor and head of the Department of Molecular Microbiology. "We've distributed the virus to researchers in Argentina,
Brazil, Mexico, Canada and, of course, all over the U.S. We have requests pending from the U.K. and Germany. Even before we published, people
heard that we were working on this and started requesting the material."
To create a model of SARS-CoV-2 that would be safer to handle, Whelan
and colleagues -- including co-senior author Michael S. Diamond, MD,
PhD, the Herbert S. Gasser Professor of Medicine, and co-first authors
Brett Case, PhD, a postdoctoral researcher in Diamond's laboratory,
and Paul W. Rothlauf, a graduate student in Whelan's laboratory
-- started with vesicular stomatitis virus (VSV). This virus is a
workhorse of virology labs because it is fairly innocuous and easy to manipulate genetically. Primarily a virus of cattle, horses and pigs,
VSV occasionally infects people, causing a mild flu-like illness that
lasts three to five days.

Viruses have proteins on their surfaces that they use to latch onto and
infect cells. The researchers removed VSV's surface-protein gene and
replaced it with the one from SARS-CoV-2, known as spike. The switch
created a new virus that targets cells like SARS-CoV-2 but lacks the
other genes needed to cause severe disease. They dubbed the hybrid
virus VSV-SARS-CoV-2.

Using serum from COVID-19 survivors and purified antibodies, the
researchers showed that the hybrid virus was recognized by antibodies
very much like a real SARS-CoV-2 virus that came from a COVID-19
patient. Antibodies or sera that prevented the hybrid virus from infecting cells also blocked the real SARS-CoV- 2 virus from doing so; antibodies
or sera that failed to stop the hybrid virus also failed to deter the
real SARS-CoV-2. In addition, a decoy molecule was equally effective at misdirecting both viruses and preventing them from infecting cells.

"Humans certainly develop antibodies against other SARS-CoV-2 proteins,
but it's the antibodies against spike that seem to be most important
for protection," Whelan said. "So as long as a virus has the spike
protein, it looks to the human immune system like SARS-CoV-2, for all
intents and purposes." The hybrid virus could help scientists evaluate
a range of antibody-based preventives and treatments for COVID-19. The
virus could be used to assess whether an experimental vaccine elicits neutralizing antibodies, to measure whether a COVID-19 survivor carries
enough neutralizing antibodies to donate plasma to COVID-19 patients,
or to identify antibodies with the potential to be developed into
antiviral drugs.

"One of the problems in evaluating neutralizing antibodies is that
a lot of these tests require a BSL-3 facility, and most clinical
labs and companies don't have BSL-3 facilities," said Diamond, who
is also a professor of molecular microbiology, and of pathology and
immunology. "With this surrogate virus, you can take serum, plasma
or antibodies and do high-throughput analyses at BSL-2 levels, which
every lab has, without a risk of getting infected. And we know that
it correlates almost perfectly with the data we get from bona fide
infectious SARS-CoV-2." Since the hybrid virus looks like SARS-CoV-2 to
the immune system but does not cause severe disease, it is a potential
vaccine candidate, Diamond added. He, Whelan and colleagues are conducting animal studies to evaluate the possibility.


========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Tamara
Bhandari. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. James Brett Case, Paul W. Rothlauf, Rita E. Chen, Zhuoming Liu,
Haiyan
Zhao, Arthur S. Kim, Louis-Marie Bloyet, Qiru Zeng, Stephen
Tahan, Lindsay Droit, Ma. Xenia G. Ilagan, Michael A. Tartell,
Gaya Amarasinghe, Jeffrey P. Henderson, Shane Miersch, Mart
Ustav, Sachdev Sidhu, Herbert W. Virgin, David Wang, Siyuan
Ding, Davide Corti, Elitza S. Theel, Daved H. Fremont, Michael
S. Diamond, Sean P.J. Whelan. Neutralizing antibody and soluble
ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a
clinical isolate of SARS-CoV-2.. Cell Host & Microbe, 2020; DOI:
10.1016/j.chom.2020.06.021 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200721162446.htm

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