US researchers have developed a new drug that could not only prevent SARS-CoV-2 and its variants, but also treat other respiratory coronaviruses in mice.
A team led by the University of Pennsylvania developed the drug diABZI, which activated the body’s innate immune response and effectively prevented severe symptoms of COVID-19, including the variant native to South Africa (B1351) and also curbed their spread in mice, the scientists said. .
Mice treated with diABZI showed much less weight loss than control mice, had significantly reduced viral loads in their lungs and nostrils, and increased cytokine production.
“Few drugs have been identified as game changers in blocking SARS-CoV-2 infection. Activating an early immune response therapeutically with a single dose is a promising strategy to control the virus, including the South African variant B1351, which has led to concern, ”said Sara Cherry, professor of pathology and medicine laboratory at the University’s Perelman School of Medicine.
“The development of effective antivirals is urgently needed to control SARS-CoV-2 infection and disease, especially as dangerous variants of the virus continue to emerge,” she added. The results are published in the journal Scientific immunology.
By observing human lung cell lines that had been infected with SARS-CoV-2, the team found that the virus is able to hide, delaying the early recognition and response of the immune system.
They performed a high-throughput screening of 75 drugs that target detection pathways in lung cells and examined their effects on viral infection under microscopy. They identified nine candidates, including two cyclic dinucleotides (CDNs), which significantly suppressed the infection by activating STING (the simulation of interferon genes).
Since CDNs are low in potency and produce mediocre drugs, according to Cherry, her team also decided to test a newly developed small-molecule STING agonist called diABZI, currently being tested in clinical trials to treat certain cancers.
Tests in mice infected with COVID-19 have shown that diABZI potently inhibits SARS-CoV-2 infection from various strains, including a variant of concern B1351, by activating STING.
In addition, diABZI could also inhibit the replication of human parainfluenza virus and rhinovirus in cultured cells. Thus, the STING agonist may be more widely effective against other respiratory viruses, the researchers said.
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