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, Ph.D., 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).
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