| First Author | Humphries F | Year | 2021 |
| Journal | Sci Immunol | Volume | 6 |
| Issue | 59 | PubMed ID | 34010139 |
| Mgi Jnum | J:333769 | Mgi Id | MGI:7435473 |
| Doi | 10.1126/sciimmunol.abi9002 | Citation | Humphries F, et al. (2021) A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection. Sci Immunol 6(59) |
| abstractText | 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. SARS-CoV-2 is a recently emerged coronavirus that has led to a global pandemic causing a severe respiratory disease known as COVID-19 with significant morbidity and mortality worldwide. The development of antiviral therapeutics are urgently needed while vaccine programs roll out worldwide. Here we describe a diamidobenzimidazole compound, diABZI-4, that activates 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 which mobilizes antiviral defenses for the treatment and prevention of COVID-19. |
