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.”

SEE ORIGINAL STUDY



Filters close

Showing results

110 of 6054
access_time Embargo lifts in 2 days
Embargo will expire: 26-Jul-2021 11:00 AM EDT Released to reporters: 23-Jul-2021 5:05 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 26-Jul-2021 11:00 AM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Newswise: NIH Chooses University of Miami Miller School of Medicine to Head Project for Its Safe Return to In-Person School Initiative
Released: 23-Jul-2021 12:15 PM EDT
NIH Chooses University of Miami Miller School of Medicine to Head Project for Its Safe Return to In-Person School Initiative
University of Miami Health System, Miller School of Medicine

The University of Miami Miller School of Medicine is helping to lead a National Institutes of Health (NIH) COVID-19 testing initiative to safely return children to in-person school.

Released: 23-Jul-2021 11:40 AM EDT
New 'Atlas' Charts How Antibodies Attack Spike Protein Variants
Brigham and Women’s Hospital

As the SARS-CoV-2 virus that causes COVID-19 continues to evolve, immunologists and infectious diseases experts are eager to know whether new variants are resistant to the human antibodies that recognized initial versions of the virus.

23-Jul-2021 8:55 AM EDT
COVID Variants and a Surge Among the Unvaccinated: Live Expert Panel for July 23rd, 2021
Newswise

Panelists will discuss the threat posed by new COVID variants and continued vaccine hesitancy.

Released: 22-Jul-2021 4:05 PM EDT
COVID-19: Patients with Malnutrition May Be More Likely to Have Severe Outcomes
Scientific Reports

Adults and children with COVID-19 who have a history of malnutrition may have an increased likelihood of death and the need for mechanical ventilation, according to a study published in Scientific Reports.

access_time Embargo lifts in 2 days
Embargo will expire: 27-Jul-2021 4:05 PM EDT Released to reporters: 22-Jul-2021 3:05 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 27-Jul-2021 4:05 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

access_time Embargo lifts in 2 days
Embargo will expire: 26-Jul-2021 4:05 PM EDT Released to reporters: 22-Jul-2021 2:45 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 26-Jul-2021 4:05 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Released: 22-Jul-2021 2:35 PM EDT
New Insights Into Uncontrolled Inflammation in COVID-19 Patients
Queen Mary University of London

In a new study, published recently in the journal Circulation Research, scientists discover how the production of protective molecules known as specialised pro-resolving mediators (SPM) is altered in patients with COVID-19.

Released: 22-Jul-2021 2:30 PM EDT
度假旅行者需要了解的COVID-19相关信息
Mayo Clinic

许多人会利用国家法定假日出门旅行或举办聚会。由于仍有许多人需要接种COVID-19疫苗以及传染性更强的Delta变种疫苗,因此健康专家建议,如果您计划旅行或召集很多人聚会,请务必谨慎。


Showing results

110 of 6054

close
1.2114