ABSTRACT
The Front Cover illustrates the natural product andrographolide, which modulates the abundance of the transcription factor NRF2, a substrate of the E3 ligase KEAP1. Previous studies identified that this drug possessed anti-SARS-CoV-2 activity, but the mechanism of action remained unclear. The authors designed and synthesized novel andrographolide derivatives with a functional site to fine-tune physicochemical properties and for linker attachment. The team assayed this new set of compounds in a cell-based NRF2 reporter gene assay and determined their ability to decrease infectivity of virus-treated Vero-E6 cells. Data showed that NRF2 activation by compounds and inhibition of SARS-CoV-2 replication correlated well. The study opens new avenues to investigate natural products that target the KEAP1/NRF2 axis as anti-SARS-CoV-2 agents. More information can be found in the Research Article by Christian Steinebach et al.