Perelman School of Medicine at the University of Pennsylvania

Researchers Discover Drug that Blocks Multiple SARS-CoV-2 Variants in Mice

Newswise — PHILADELPHIA – The drug diABZI — which activates the body’s innate immune response — was highly effective in preventing severe COVID-19 in mice that were infected with SARS-CoV-2, according to scientists in the Perelman School of Medicine at the University of Pennsylvania. The findings, published this month in Science Immunology, suggest that diABZI could also treat other respiratory coronaviruses.

“Few drugs have been identified as game-changers in blocking SARS-CoV-2 infection. This paper is the first to show that activating an early immune response therapeutically with a single dose is a promising strategy for controlling the virus, including the South African variant B.1.351, which has led to worldwide concern,” said senior author Sara Cherry, PhD, a professor of Pathology and Laboratory Medicine and scientific director of the High-Throughput Screening (HTS) Core at Penn Medicine. “The development of effective antivirals is urgently needed for controlling SARS-CoV-2 infection and disease, especially as dangerous variants of the virus continue to emerge.”

The SARS-CoV-2 virus initially targets epithelial cells in the respiratory tract. As the first line of defense against infection, the respiratory tract’s innate immune system recognizes viral pathogens by detecting their molecular patterns. Cherry and her research team first sought to better understand this effect by observing human lung cell lines under the microscope that had been infected with SARS-CoV-2. They found that the virus is able to hide, delaying the immune system’s early recognition and response. The researchers predicted that they may be able to identify drugs — or small molecules with drug-like properties — that could set off this immune response in the respiratory cells earlier and prevent severe SARS-CoV-2 infection.

To identify antiviral agonists that would block SARS-CoV-2 infection, the researchers performed high throughput screening of 75 drugs that target sensing pathways in lung cells. They examined their effects on viral infection under microscopy and identified nine candidates —including two cyclic dinucleotides (CDNs) — that significantly suppressed infection by activating STING (the simulation of interferon genes).

Since CDNs have low potency and make poor drugs, according to Cherry, she and her team decided to also test a newly-developed small molecule STING agonist called diABZI, which is not approved by the Food and Drug Administration but is currently being tested in clinical trials to treat some cancers. The researchers found that diABZI potently inhibits SARS-CoV-2 infection of diverse strains, including variant of concern B.1.351, by stimulating interferon signaling.              Finally, the researchers tested the effectiveness of diABZI in transgenic mice that had been infected with SARS-CoV-2. Because the drug needed to reach the lungs, diABZI was administered through a nasal delivery. diABZI-treated mice showed much less weight loss than the control mice, had significantly-reduced viral loads in their lungs and nostrils, and increased cytokine production — all supporting the finding that diABZI stimulates interferon for protective immunity.

Cherry said that the study’s findings offer promise that diABZI could be an effective treatment for SARS-CoV-2 that could prevent severe COVID-19 symptoms and the spread of infection. Additionally, since diABZI has been shown to inhibit human parainfluenza virus and rhinovirus replication in cultured cells, the STING agonist may be more broadly effective against other respiratory viruses.

“We are now testing this STING agonist against  many other viruses,” Cherry said. “It’s really important to remember that SARS-CoV-2 is not going to be the last coronavirus that we will see and will need protection against.”

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Newswise: Public
Released: 28-Jul-2021 2:45 PM EDT
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Newswise: Public
Released: 28-Jul-2021 2:20 PM EDT
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Released: 28-Jul-2021 2:10 PM EDT
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VIDEO
Released: 28-Jul-2021 1:40 PM EDT
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Released: 28-Jul-2021 12:50 PM EDT
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Released: 28-Jul-2021 12:00 PM EDT
MD Anderson Research Highlights for July 28, 2021
University of Texas M. D. Anderson Cancer Center

The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recently published studies in basic, translational and clinical cancer research from MD Anderson experts. Current advances include a newly discovered protein that controls B cell survival, understanding epigenetic changes in malignant peripheral nerve sheath tumors (MPNSTs) and melanoma, identifying a protein that protect genome stability, developing novel cell therapies for COVID-19, a new option for treating neuropathic pain, exosome delivery of CRISPR/Cas9 to pancreatic cancer, discovering how cancer cells tolerate aneuploidy and the role of health disparities in long-term survival of adolescent and young adult patients with Hodgkin lymphoma.

Released: 28-Jul-2021 11:30 AM EDT
Study Reveals Characteristics of SARS-CoV-2 Spike Protein
University of Kentucky

A new University of Kentucky College of Medicine study published in the Journal of Biological Chemistry provides foundational information about SARS-CoV-2’s spike protein.

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Newswise: UIC Awarded $6 Million to Develop Potential COVID-19 Treatment
Released: 28-Jul-2021 10:15 AM EDT
UIC Awarded $6 Million to Develop Potential COVID-19 Treatment
University of Illinois Chicago

Researchers at the University of Illinois Chicago are developing a potential treatment for COVID-19, thanks to a $6 million technology and therapeutic development award from the U.S. Department of Defense supporting pre-clinical animal studies.

Newswise: Don’t Let the Raging Virus Put Life in Jeopardy. Chula Recommends How to Build an Immunity for Your Heart Against Stress and Depression
Released: 28-Jul-2021 8:55 AM EDT
Don’t Let the Raging Virus Put Life in Jeopardy. Chula Recommends How to Build an Immunity for Your Heart Against Stress and Depression
Chulalongkorn University

Cumulative stress, denial, and chronic depression are the byproducts of the COVID-19 pandemic. The Center for Psychological Wellness, Chulalongkorn University recommends ways to cope by harnessing positive energy from our heart.


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