'Decoy' protein works against multiple SARS-CoV-2 variants, researchers
report

Date:
January 19, 2022
Source:
University of Illinois Chicago
Summary:
A drug treatment that acts as a decoy against SARS-CoV-2 was highly
effective at preventing death and lung damage in humanized animal
models of severe COVID-19 disease. The study suggests that the drug
has the potential to treat COVID-19 patients, including those who
are infected with aggressive SARS-CoV-2 variants.



FULL STORY ==========================================================================
A drug treatment that acts as a decoy against SARS-CoV-2 was highly
effective at preventing death and lung damage in humanized animal models
of severe COVID- 19 disease, according to a Nature Chemical Biology
study from researchers at the University of Illinois Chicago. The study suggests that the drug has the potential to treat COVID-19 patients,
including those who are infected with aggressive SARS-CoV-2 variants.


==========================================================================
The study's senior lead author is Asrar Malik, professor in the
department of pharmacology and regenerative medicine at the UIC College
of Medicine. Jalees Rehman, professor in the department of pharmacology
and regenerative medicine and the department of medicine, is a co-lead
author of the study, "Engineered ACE2 decoy mitigates lung injury and
death induced by SARS-CoV-2 variants." "While vaccines remain the best
option for preventing infections, long-term complications and death
from COVID-19, there is an urgent need for the development of effective treatments for vulnerable patients, especially as new variants continue
to arise," Rehman said.

"Vulnerable individuals who are at risk of developing severe COVID-19
include those who are unvaccinated or immunocompromised and therefore
their immune system cannot protect them as well even after receiving vaccinations and boosters," he said. "In addition, new variants of
SARS-CoV-2, such as the most recent omicron variant, may partially
evade the immune system and can cause breakthrough infections. For
all the vulnerable patients, we need to create an array of treatments
so that health care providers can choose the most appropriate drug
or combination of drugs, depending on the individual patient's disease
stage and severity." The drug treatment, developed through a partnership between UIC and the University of Illinois Urbana-Champaign, consists
of an artificially engineered ACE2 protein designed with unprecedently
high binding capacity for the spike protein of SARS-CoV-2, which binds
to natural ACE2 protein receptors located on human cells and causes
COVID-19. The drug works by competing for the spike protein and soaking
up viruses before they can bind and enter cells.

In animal studies of severe COVID-19, the researchers used mouse
models designed to carry the human ACE2 protein. With multiple treatment regimens, infected mice were given the drug intravenously. The researchers found that mice receiving the treatment showed markedly reduced death
and no significant evidence of severe acute respiratory syndrome, the
hallmark of the disease and primary cause of death. The mice receiving
the drug also regained appetite and weight, which are signs of recovery.



==========================================================================
The benefits were seen even when mice were exposed to the aggressive
gamma variant, suggesting the drug's broad applicability against newly
emerging COVID-19 variants.

"The reduced rates of fluid buildup in the lungs and of death in treatment group illustrates the potential of the ACE2 decoy to help people with
severe COVID-19," Malik said. Severe fluid buildup in the lung is one
of the complications of COVID-19 that makes it difficult for patients
to breathe and leads to the need for a ventilator.

In additional studies, the researchers tested how well the decoy would
bind and neutralize multiple variants of SARS-CoV-2. They observed that
the decoy was able to bind to the spike proteins from all the variants
tested, which included the alpha, beta, gamma, delta and epsilon variants, which were available at the time of the study. They also found that it
bound equally, if not better, to the variants than it did to the original strain of the virus.

"Considering the emergence of omicron, it is very good news that the
ACE2 decoy was able to bind and neutralize several variants, and this reinforces the potential of this drug as a treatment, including against
new or future variants of the virus," Rehman said.

One of the exciting things about the drug, Rehman said, is that it has
the potential to be used in combination with other drugs, especially
those that prevent replication of the virus that has already entered
cells or drugs that prevent an excessive immune response, which itself
can worsen COVID-19 complications.



==========================================================================
The researchers also found that the decoy protein could be delivered by inhalation directly to the lungs of mice.

Even though many of the treated animals recovered, a few mice developed
lung scarring over time. According to the researchers, this highlights
the importance of also studying and developing therapies for long-term
COVID-19 complications, such as long COVID.

The research was funded in part by grants from the National Institutes of Health (P01HL060678, P01HL151327, R01HL154538, R01HL152515. R43AI162329, R01HL157489, T32HL007829).

UIC's Lianghui Zhang, assistant professor in the department of
pharmacology and regenerative medicine, and UIUC's Erik Procko, associate professor in the department of biochemistry, are also co-lead authors
of the study.

Additional co-authors of the paper are Shiqin Xiong, Matthew Lindeblad,
Laura Cooper, Lijun Rong, Anthony Gugliuzza, Soumajit Dutta, Matthew Chan, Timothy Fan, Keith Bailey, Diwakar Shukla and Kui Chan.

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


========================================================================== Journal Reference:
1. Lianghui Zhang, Soumajit Dutta, Shiqin Xiong, Matthew Chan, Kui
K. Chan,
Timothy M. Fan, Keith L. Bailey, Matthew Lindeblad, Laura M. Cooper,
Lijun Rong, Anthony F. Gugliuzza, Diwakar Shukla, Erik Procko,
Jalees Rehman, Asrar B. Malik. Engineered ACE2 decoy mitigates lung
injury and death induced by SARS-CoV-2 variants. Nature Chemical
Biology, 2022; DOI: 10.1038/s41589-021-00965-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220119142828.htm

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