AHR activation during viral infection results in the upregulation of IDO/TDO, which convert tryptophan to Kynurenine (Kyn). Kyn activates AHR, leading to formation of an AHR–ligand complex that limits host anti-viral responses mediated by IFN-I and NF-κB, thus promoting viral replication. AHR signaling also induces mucin expression in lung epithelial cells, thickening the blood–air barrier, impairing O2 diffusion and causing hypoxia. AHR antagonists limit AHR activation, boosting the host anti-viral response and consequently reducing viral replication. AHR antagonism also reduces the expression of mucins, limiting lung pathology during SARS-CoV-2 infection.