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New drug effective at preventing severe COVID-19 in SARS-CoV-2-infected mice



Scientists at the Perelman School of Medicine at the University of Pennsylvania say that diABZI, which stimulates the body’s innate immune response, has been shown to increase the immune system. It was highly effective at preventing severe COVID-19 in SARS-CoV-2-infected mice, findings published this month in Scientific Reports. immunologysuggest that diABZI can treat coronaviruses other airways as well

Few drugs have been identified as game-changers in blocking SARS-CoV-2 infection. This paper is the first report showing that it also stimulates early immune responses. A single dose is a promising strategy for controlling the virus. This includes the South African variant B.1

.351. which has led to worldwide concern. The development of effective antiviral drugs is urgently needed to control SARS-CoV-2 infection and disease, especially when harmful strains of the virus are still present.

Sara Cherry, PhD, senior author on the study and professor of pathology and laboratory medicine and director of science, High-Throughput Screening Core, Penn Medicine.

SARS-CoV-2 virus initially targets respiratory epithelial cells. As the first line of defense against infection The innate immune system of the respiratory system recognizes viral pathogens by detecting their molecular forms.

Sherry and her research team sought to better understand this effect by observing human lung cell lines under a microscope infected with SARS-CoV-2. This slows the perception and response of the immune system. The researchers speculated that they might be able to identify the drug. or small molecules with drug-like properties which can trigger an immune response in earlier respiratory cells. and preventing severe SARS-CoV-2 infection.

To identify antiviral catalysts that would prevent SARS-CoV-2 infection, researchers screened 75 high-throughput drugs that target detection pathways in lung cells. They examined the effects on viral infection under a microscope and identified nine candidates, including two cyclic dinucleotides (CDNs), which significantly inhibited infection by reactivating the virus. STING task (interferon gene simulation)

This is because CDNs are ineffective and poorly produced drugs. So she and her team decided to test a newly developed small molecule STING catalyst called diABZI, which has not been approved by the Food and Drug Administration. But it is currently undergoing clinical testing. some cancer treatment trials Researchers found that diABZI inhibited SARS-CoV-2 infection of various strains. effectively including the variant of concern B.1.351 by stimulating the interferon signal.

Finally, the researchers tested the efficacy of diABZI in SARS-CoV-2-infected genetically engineered mice. Because the drug needed to reach the lungs, diABZI was administered through a nasal delivery. The diABZI-treated mice showed less weight loss than the control mice. There was a significant reduction in the amount of virus in the lungs and sinuses. and increase cytokine production All of which support the finding that diABZI stimulates interferon for immune defenses.

Cherry said the results of the study promise that diABZI could be an effective treatment for SARS-CoV-2. This can prevent the severe symptoms of COVID-19 and the spread of infection. parainfluenza In humans and rhinovirus replication in cultured cells, the STING agonist may be more broadly effective against other respiratory viruses.

“We are currently testing this STING protagonist against other viruses. “It is important to remember that SARS-CoV-2 will not be the last coronavirus we will see and must be protected.”

Source:

University of Pennsylvania School of Medicine

Journal Reference:

Li, M, et al. (2021) Pharmacological activation of STING blocks SARS-CoV-2 infection. immunology. doi.org/10.1126/sciimmunol.abi9007.


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