Sci. Immunol. https://doi.org/10.1126/sciimmunol.abi9007 (2021)

Sci. Immunol. https://doi.org/10.1126/sciimmunol.abi9002 (2021)

Antiviral Res. https://doi.org/10.1016/j.antiviral.2021.105015 (2021)

The ability of SARS-CoV-2 to avoid the immune system is thought to be a result, in part, of inefficient or misdirected antiviral signaling responses. In January, Zhu et al. published in Antiviral Research that the potent small molecule STING agonist diABZI can boost interferon signaling to limit the replication of SARS-CoV-2 in primary human airway epithelial air–liquid interface cultures via TBK1–IRF signaling. Two papers now published back-to-back in Science Immunology show the same thing but push these findings in vivo, with potential clinical implications. Both Humphries et al. and Li et al. could prevent respiratory disease in SARS-CoV-2-infected ACE2-transgenic mice with a single intranasal dose of diABZI, administered either before or after infection. Additionally, Li et al. showed that diABZI has antiviral activity against the variant of concern B.1.351, commonly referred to as the variant first detected in South Africa, and now as the Beta variant, according to recent WHO nomenclature guidelines. The broad and potent activity of diABZI, along with the efficacy of intranasal delivery, indicate that it is a decent candidate for human trials.