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.
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. o 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 can 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 a 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, the scientists tested 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 a 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.
Ref link: doi.org/10.1126/sciimmunol.abi9007
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