Pharmacological modulators of epithelial immunity uncovered by synthetic genetic tracing of SARS-CoV-2 infection responses.

ABSTRACT: Epithelial immune responses govern tissue homeostasis and offer drug targets against maladaptation. Here, we report a framework to generate drug discovery-ready reporters of cellular responses to viral infection. We reverse-engineered epithelial cell responses to SARS-CoV-2, the viral agent fueling the ongoing COVID-19 pandemic, and designed synthetic transcriptional reporters whose molecular logic comprises interferon-α/β/γ and NF-κB pathways. Such regulatory potential reflected single-cell data from experimental models to severe COVID-19 patient epithelial cells infected by SARS-CoV-2. SARS-CoV-2, type I interferons, and RIG-I drive reporter activation. Live-cell image-based phenotypic drug screens identified JAK inhibitors and DNA damage inducers as antagonistic modulators of epithelial

SUBMITTER: Jiang B 

PROVIDER: S-EPMC10284557 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature