Fig. 1.

Schematic presentation of the systematic perturbation in TRP and KYN metabolism during SARS-CoV-2 infection. SARS-CoV-2 infection of the nasal-olfactory epithelium is associated with downregulation of ACE2 and upregulation of ACE-Ang II-AT1R activity along with local innate immune response and release of proinflammatory cytokines. This results in increased expression of IDO activity in the nasal epithelium resulting in perturbation of TRP metabolism towards KYN metabolites, while serotonin synthesis is reduced. Blue boxes indicate neuroprotective KYN metabolites that decreases in SARS-CoV-2 infected patients; red boxes indicate the neurotoxic metabolites that significantly increase following SARS-CoV-2 infection. Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE, angiotensin converting enzyme; Ang II, angiotensin II; AT1R, angiotensin type 1 receptor; IFN-γ, interferon-γ; IFN- α, interferon-α; TNF-α, tumor necrosis factor-α; IDO1, indoleamine-2,3-dioxygenase 1; IDO2, indoleamine-2,3-dioxygenase 2; TRP, tryptophan; KYN, kynurenine; 3-HK, 3-hydroxykynurenine; KA, kynurenic acid; QA, quinolinic acid; NAD, nicotinamide adenine dinucleotide; KAT, kynurenine aminotransferase; KMO, kynurenine 3-monooxygenase; KYNU, kynurenine hydroxylase; QPRT, quinolinic acid phosphoribosyltransferase; SIRT, sirtuin deacetylase. Solid lines represent pathways that are predominant and dash lines represent pathways with reduced activity. Red cross represents enzymatic activities that are specifically reduced in SARS-CoV-2 infection.