The Bridge - Issue 1, 2021 - 8

Feature

Oak Ridge National Laboratory Staff Mobilize to Combat Novel Coronavirus

Advanced materials
Collaborators at ORNL's Center for Nanophase
Materials Sciences (a DOE Office of Science user
facility) and the University of Tennessee Health
Science Center are developing a breath-sampling
whistle that could make COVID-19 screening easy
to do at home.
ORNL and researchers partnered to design the
device as an at-home alternative to traditional
diagnostics, such as nasal swabs, with a goal to
inform decisions on health and safety.
" Our motivation is to put actionable information
in the hands of users to help them make timely
decisions, such as whether to go to work or school,
quarantine, or seek medical care, " said University
of Tennessee Health Science Center's Dr.
Scott Strome.
The technology makes use of a familiar concept-
a whistle-to capture aerosols from exhaled breath.
Testers simply blow the whistle to make an audible
sound. An app that monitors breathing rate
may be integrated to help users operate the
device correctly (Figure 3).
Inside the whistle, a unique hydrogel material
preserves breath samples for later testing. These
samples could either be sent to a lab for analysis
or, preferably, transferred to an accompanying test
kit that could detect the SARS-CoV-2 virus that
causes COVID-19.

Figure 3: Collaborators at Oak Ridge National Laboratory and the
University of Tennessee Health Science Center are developing a breathsampling whistle that could make COVID-19 screening easy to do at
home. Credit: Michelle Lehman/ORNL, U.S. Dept. of Energy.

THE BRIDGE

Oak Ridge National Laboratory Staff Mobilize to Combat Novel Coronavirus

products that are currently being investigated by
medical experts as possible treatments for mitigating
COVID-19 symptoms. This change could potentially
make membrane intrusions more challenging for viral
spike proteins.

" Our aim is for a complete at-home approach with
a simple and robust test that could be used by
anyone, " said ORNL's Scott Retterer.
Ease of use makes the testing format suitable for a
broad range of users, including children and elderly,
and the simple design adds to scalability. Prototype
whistles are 3D printed from a resin material but
could also be molded for low-cost mass production.
This research was supported by the DOE Office of
Science through the National Virtual Biotechnology
Laboratory, a consortium of DOE national
laboratories focused on response to COVID-19, with
funding provided by the Coronavirus CARES Act.

Building a molecular picture
Researchers from Virginia Tech and ORNL are using
neutron scattering to investigate how the virus
infiltrates host cells and what therapeutics could help
inhibit this process. Such information could help
experts design strategies to slow the progress of viral
infection and reduce its harmful effects.
Part of the team's study involves examining some of
the biological tools the virus employs to infect host
cells. This includes their spike proteins, barb-like
proteins on the surface of the virus that initiate the
infection process, and E-proteins, which help the virus
replicate itself inside the cell and can trigger acute
inflammation in the host's lungs.
Another aspect of this research is focused on the cell
membrane, which serves as the cell's outermost line
of defense against the virus (Figure 4). The scientists
aim to better understand how cell membranes
change when they encounter spike proteins and
what therapeutic candidates could make them more
resistant to viral entry.
This project tapped into the wide range of expertise
within the laboratory. " At ORNL we are able to work
with experts from many fields, such as physics,
chemistry, and biology, " said ORNL's Jessy Labbé,
a cellular and molecular geneticist involved in this
study. " When the crisis began, we applied this
combined knowledge to develop research projects
that address some of the biggest challenges related
to the pandemic. "

Feature

Figure 4: The cell membrane is the cell's first line of defense against
the coronavirus responsible for COVID-19. The virus uses its spike
proteins and E-proteins to penetrate the cell membrane and create
copies of itself within the cell. Researchers are investigating how this
process works and what treatments can help to stop it. Credit: ORNL/
Jill Hemman.

The team is using the liquids reflectometer (LIQREF)
at ORNL's Spallation Neutron Source to examine the
conformation of membranes and viral proteins, as
well as the effects of certain therapeutic candidates.
With the instrument, scientists can measure the
trajectories of neutrons as they interact with different
biological materials. They then use this information
to determine how a sample is organized at the
molecular level.
" Neutrons are highly penetrating and nondestructive
particles, allowing our team to explore how these
biological materials operate at the molecular level
without damaging them. Such information could help
experts develop strategies for slowing the spread of
infection within patients and mitigating the severity of
the disease, " said Labbé.
The researchers performed their experiments with a
membrane model that closely mirrors the shape and
composition of cell membranes within human lungs,
where respiratory viral infections primarily take place.
Using LIQREF, the team first characterized the
membrane's original structure. They then introduced
the spike protein or E-protein to the membranes
and analyzed how these structures change shape
when they interact. They also measured how the
membrane's properties change when exposed to
either melatonin or azithromycin-commonly available

The initial results suggest that membranes pack
more closely together when introduced to melatonin
or azithromycin. Furthermore, they demonstrated
that the readily available and approved inhibitor,
amantadine, significantly affects the interaction
between the cell membrane and E-protein. Their
findings suggest that the inhibitor should be further
investigated as a potential therapy to combat the
virus's lethality.
Going forward, the researchers envision these
methods could be used to rapidly and systemically
screen treatment candidates for the COVID-19
pandemic and future viral respiratory threats.

Pandemic modeling and analysis
Argonne, Oak Ridge, Los Alamos, and Sandia
National Laboratories are collaborating to develop an
integrated COVID-19 pandemic monitoring, modeling,
and analysis expertise, leveraging the labs' collective
scalable data and computing.
Geographic data scientists at ORNL continue to track
reported COVID-19 outbreaks by maintaining a series
of maps that monitor the speed of transmission and
rate of growth across all 50 U.S. states and their
more than 3,300 total counties, as well as across
nearly 250 countries worldwide. The map draws on
ORNL's foundational population distribution databases,
LandScan USA and LandScan Global (Figure 5).
A model built with this data and developed in
collaboration with the University of Tennessee
provides seven-day forecasts, updated daily, of new
case counts with confidence intervals for every county
in the United States. The first seven-day forecast was
produced in June, using ORNL's Compute and
Data Environment for Science high-performance
computing resources.
" We wanted to provide that situational awareness
for county-level decisionmakers on what to expect,
so they can allocate resources and structure

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The Bridge - Issue 1, 2021

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