New drug effectively inhibits severe COVID-19 in SARS-CoV-2-infected mice


The drug diABZI activates the body’s natural immune response-very effective in preventing severe COVID-19 in mice infected with SARS-CoV-2, according to scientists at the Perelman School of Medicine at the University of Pennsylvania . The findings, published this month on Science Immunology, suggested that diABZI may also treat other respiratory conditions coronaviruses.

Very few drugs have been identified as game-changers in preventing SARS-CoV-2 infection. This paper is the first to show that activating early resistance to treatment therapeutically with a single dose is a good approach for controlling viruses, including the South African variant B.1.351, which has led to concern. all over the world. The development of effective antiviruses is urgently needed for the prevention of SARS-CoV-2 infection and disease, especially as the risks that the virus continues to emerge. “

Sara Cherry, PhD, Study Senior Author and Professor of Pathology and Laboratory Medicine and Scientific Director, High-Throughput Screening Core, Penn Medicine

The SARS-CoV-2 virus primarily targets epithelial cells in the respiratory tract. As the first line of defense against infection, the innate immune system of the respiratory tract recognizes viral pathogens by recognizing their molecular patterns.

Cherry and her researcher first sought to better understand this effect by observing human lung cell lines under the microscope infected with SARS-CoV-2. They found that the virus was able to hide, delaying the early detection and response of the immune system. The researchers predict that they may be able to identify drugs – or small molecules with drug -like properties – that could suppress this immune response of respiratory cells and prevent severe infection in SARS-CoV-2.

To identify antiviral agonists that can prevent SARS-CoV-2 infection, the researchers conducted a lengthy review 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 are important in preventing infection by activating STING (the simulation of interferon genes). .

Because CDNs have little potency and produce bad drugs, according to Cherry, she and her group decided to also try a newly developed small molecule STING agonist called diABZI, which did not. approved by the Food and Drug Administration but is now testing clinical trials to treat some cancers. The researchers found that diABZI strongly inhibits SARS-CoV-2 infection in a variety of species, including the B.1.351 strain, by stimulating the interferon signal.

Finally, the researchers tested the efficacy of diABZI in transgenic mice infected with SARS-CoV-2. Because the drug is needed to reach the lungs, diABZI is administered by nasal delivery. Mice treated with diABZI showed less weight gain than control mice, reduced multiple viral loads in their lungs and nostrils, and increased cytokine production-all. which supports the finding that diABZI activates interferon for protective resistance.

Cherry said the findings of the study suggest that diABZI could be an effective treatment for SARS-CoV-2 that avoids severe COVID-19 symptoms and the spread of infection. In addition, because diABZI has been shown to inhibit human parainfluenza virus and the replication of rhinovirus in cultured cells, the STON agonist may have a much broader effect 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 may not be the last coronavirus we see and will need protection against.”

Origin:

Please refer to the journal:

Li, M., and so on. (2021) Drug activation of STING inhibits SARS-CoV-2 infection. Science Immunology. doi.org/10.1126/sciimmunol.abi9007.



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