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- Title
A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection.
- Authors
Humphries, Fiachra; Shmuel-Galia, Liraz; Jiang, Zhaozhao; Wilson, Ruth; Landis, Philip; Ng, Sze-Ling; Parsi, Krishna Mohan; Maehr, Rene; Cruz, John; Morales, Angel; Ramanjulu, Joshi M.; Bertin, John; Pesiridis, G. Scott; Fitzgerald, Katherine A.
- Abstract
Coronaviruses are a family of RNA viruses that cause acute and chronic diseases of the upper and lower respiratory tract in humans and other animals. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged coronavirus that has led to a global pandemic, causing a severe respiratory disease known as coronavirus disease 2019 (COVID-19) with substantial morbidity and mortality worldwide. The development of antiviral therapeutics is urgently needed while vaccine programs roll out worldwide. Here, we describe a diamidobenzimidazole compound, diABZI-4, that activates stimulator of interferon genes (STING) and is highly effective in limiting SARS-CoV-2 replication in cells and animals. diABZI-4 inhibited SARS-CoV-2 replication in lung epithelial cells. Administration of diABZI-4 intranasally before or even after virus infection conferred complete protection from severe respiratory disease in K18-ACE2 transgenic mice infected with SARS-CoV-2. Intranasal delivery of diABZI-4 induced a rapid short-lived activation of STING, leading to transient proinflammatory cytokine production and lymphocyte activation in the lung associated with inhibition of viral replication. Our study supports the use of diABZI-4 as a host-directed therapy that mobilizes antiviral defenses for the treatment and prevention of COVID-19.
- Publication
Science Immunology, 2021, Vol 6, Issue 59, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abi9002