Fischer WA 2nd, Gong M, Bhagwanjee S, Sevransky J. Global burden of influenza as a cause of cardiopulmonary morbidity and mortality. Glob Heart. 2014;9(3):325–36.
Javanian M, Barary M, Ghebrehewet S, Koppolu V, Vasigala V, Ebrahimpour S. A brief review of influenza virus infection. J Med Virol. 2021;93(8):4638–46.
Uyeki TM, Hui DS, Zambon M, Wentworth DE, Monto AS. Influenza. Lancet. 2022;400(10353):693–706.
Dadashi M, Khaleghnejad S, Abedi Elkhichi P, Goudarzi M, Goudarzi H, Taghavi A, et al. COVID-19 and Influenza co-infection: a systematic review and meta-analysis. Front Med. 2021;8:681469.
Flerlage T, Boyd DF, Meliopoulos V, Thomas PG, Schultz-Cherry S. Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract. Nat Rev Microbiol. 2021;19(7):425–41.
Chen X, Liu S, Goraya MU, Maarouf M, Huang S, Chen JL. Host immune response to influenza A virus infection. Front Immunol. 2018;9:320.
Chen Y, Michalak M, Agellon LB. Importance of nutrients and nutrient metabolism on human health. Yale J Biol Med. 2018;91(2):95–103.
Tian X, Zhang K, Min J, Chen C, Cao Y, Ding C, Liu W, Li J. Metabolomic analysis of influenza A virus A/WSN/1933 (H1N1) infected A549 cells during first cycle of viral replication. Viruses. 2019;11(11):1007.
Keshavarz M, Solaymani-Mohammadi F, Namdari H, Arjeini Y, Mousavi MJ, Rezaei F. Metabolic host response and therapeutic approaches to influenza infection. Cell Mol Biol Lett. 2020;25:15.
van Liempd S, Cabrera D, Pilzner C, Kollmus H, Schughart K, Falcón-Pérez JM. Impaired beta-oxidation increases vulnerability to influenza A infection. J Biol Chem. 2021;297(5):101298.
Thomas S, Ouhtit A, Al Khatib HA, Eid AH, Mathew S, Nasrallah GK, et al. Burden and disease pathogenesis of influenza and other respiratory viruses in diabetic patients. J Infect Public Health. 2022;15(4):412–24.
Pang Z, Zhou G, Chong J, Xia J. Comprehensive meta-analysis of COVID-19 global metabolomics datasets. Metabolites. 2021;11(1):44.
Chi H. Immunometabolism at the intersection of metabolic signaling, cell fate, and systems immunology. Cell Mol Immunol. 2022;19(3):299–302.
Sumbria D, Berber E, Mathayan M, Rouse BT. Virus Infections and host metabolism-can we manage the interactions? Front Immunol. 2020;11:594963.
Lawler NG, Gray N, Kimhofer T, Boughton B, Gay M, Yang R, et al. Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses. J Proteome Res. 2021;20(5):2796–811.
Melano I, Kuo LL, Lo YC, Sung PW, Tien N, Su WC. Effects of basic amino acids and their derivatives on SARS-CoV-2 and influenza-A virus infection. Viruses. 2021;13(7):1301.
Wang X, Zhu J, Zhang D, Liu G. Ribosomal control in RNA virus-infected cells. Front Microbiol. 2022;13:1026887.
Yang L, Chu Z, Liu M, Zou Q, Li J, Liu Q, et al. Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy. J Hematol Oncol. 2023;16(1):59.
Wirusanti NI, Baldridge MT, Harris VC. Microbiota regulation of viral infections through interferon signaling. Trends Microbiol. 2022;30(8):778–92.
Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-tryptophan: basic metabolic functions, behavioral research and therapeutic indications. Int J Tryptophan Res. 2009;2:45–60.
Kanova M, Kohout P. Tryptophan: a unique role in the critically ill. Int J Mol Sci. 2021;22(21):11714.
Almulla AF, Supasitthumrong T, Tunvirachaisakul C, Algon AAA, Al-Hakeim HK, Maes M. The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis. BMC Infect Dis. 2022;22(1):615.
Schuller M, Oberhuber M, Prietl B, Zügner E, Prugger EM, Magnes C, et al. Alterations in the kynurenine-tryptophan pathway and lipid dysregulation are preserved features of COVID-19 in hemodialysis. Int J Mol Sci. 2022;23(22):14089.
Essa MM, Hamdan H, Chidambaram SB, Al-Balushi B, Guillemin GJ, Ojcius DM, et al. Possible role of tryptophan and melatonin in COVID-19. Int J Tryptophan Res. 2020;13:1178646920951832.
Vyavahare S, Kumar S, Cantu N, Kolhe R, Bollag WB, McGee-Lawrence ME, et al. Tryptophan-kynurenine pathway in COVID-19-dependent musculoskeletal pathology: a minireview. Mediators Inflamm. 2021;2021:2911578.
Eroğlu İ, Eroğlu BÇ, Güven GS. Altered tryptophan absorption and metabolism could underlie long-term symptoms in survivors of coronavirus disease 2019 (COVID-19). Nutrition. 2021;90:111308.
Wishart DS. Metabolomics for investigating physiological and pathophysiological processes. Physiol Rev. 2019;99(4):1819–75.
DeBerardinis RJ, Keshari KR. Metabolic analysis as a driver for discovery, diagnosis, and therapy. Cell. 2022;185(15):2678–89.
Hasan MR, Suleiman M, Pérez-López A. Metabolomics in the diagnosis and prognosis of COVID-19. Front Genet. 2021;12:721556.
Wendt CH, Castro-Pearson S, Proper J, Pett S, Griffin TJ, Kan V, et al. Metabolite profiles associated with disease progression in influenza infection. PLoS ONE. 2021;16(4):e0247493.
Hu D, Al-Shalan HAM, Shi Z, Wang P, Wu Y, Nicholls PK, et al. Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining. Sci Rep. 2020;10(1):9850.
Al-Shalan HAM, Hu D, Nicholls PK, Greene WK, Ma B. Immunofluorescent characterization of innervation and nerve-immune cell neighborhood in mouse thymus. Cell Tissue Res. 2019;378(2):239–54.
Klein Wolterink RGJ, Wu GS, Chiu IM, Veiga-Fernandes H. Neuroimmune interactions in peripheral organs. Annu Rev Neurosci. 2022;45:339–60.
Kelly B, Pearce EL. Amino assets: how amino acids support immunity. Cell Metab. 2020;32(2):154–75.
Li P, Wu G. Important roles of amino acids in immune responses. Br J Nutr. 2022;127(3):398–402.
Sato H, Takado Y, Toyoda S, Tsukamoto-Yasui M, Minatohara K, Takuwa H, et al. Neurodegenerative processes accelerated by protein malnutrition and decelerated by essential amino acids in a tauopathy mouse model. Sci Adv. 2021;7(43):eabd5046.
Pashaei S, Yarani R, Mohammadi P, Emami Aleagha MS. The potential roles of amino acids and their major derivatives in the management of multiple sclerosis. Amino Acids. 2022;54(6):841–58.
Strickland DH, Fear V, Shenton S, Wikstrom ME, Zosky G, Larcombe AN, et al. Persistent and compartmentalised disruption of dendritic cell subpopulations in the lung following influenza A virus infection. PLoS ONE. 2014;9(11):e111520.
Darnell ME, Subbarao K, Feinstone SM, Taylor DR. Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV. J Virol Methods. 2004;121(1):85–91.
Gray N, Lawler NG, Yang R, Morillon AC, Gay MCL, Bong SH, et al. A simultaneous exploratory and quantitative amino acid and biogenic amine metabolic profiling platform for rapid disease phenotyping via UPLC-QToF-MS. Talanta. 2021;223(Pt 2):121872.
Boughton BA, Callahan DL, Silva C, Bowne J, Nahid A, Rupasinghe T, et al. Comprehensive profiling and quantitation of amine group containing metabolites. Anal Chem. 2011;83(19):7523–30.
Makowski L, Chaib M, Rathmell JC. Immunometabolism: from basic mechanisms to translation. Immunol Rev. 2020;295(1):5–14.
Jang H, Boltz D, Sturm-Ramirez K, Shepherd KR, Jiao Y, Webster R, et al. Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration. Proc Natl Acad Sci USA. 2009;106(33):14063–8.
Hosseini S, Wilk E, Michaelsen-Preusse K, Gerhauser I, Baumgärtner W, Geffers R, et al. Long-term neuroinflammation induced by influenza a virus infection and the impact on hippocampal neuron morphology and function. J Neurosci. 2018;38(12):3060–80.
Khandaker G, Zurynski Y, Buttery J, Marshall H, Richmond PC, Dale RC, et al. Neurologic complications of influenza A(H1N1)pdm09: surveillance in 6 pediatric hospitals. Neurology. 2012;79(14):1474–81.
Hosseini S, Michaelsen-Preusse K, Schughart K, Korte M. Long-term consequence of non-neurotropic H3N2 influenza A virus infection for the progression of Alzheimer’s disease symptoms. Front Cell Neurosci. 2021;15:643650.
Hara H, Chida J, Uchiyama K, Pasiana AD, Takahashi E, Kido H, et al. Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells. Sci Rep. 2021;11(1):10109.
Su Y, Barr J, Jaquish A, Xu J, Verheyden JM, Sun X. Identification of lung innervating sensory neurons and their target specificity. Am J Physiol Lung Cell Mol Physiol. 2022;322(1):L50-l63.
De Virgiliis F, Di Giovanni S. Lung innervation in the eye of a cytokine storm: neuroimmune interactions and COVID-19. Nat Rev Neurol. 2020;16(11):645–52.
Belvisi MG. Overview of the innervation of the lung. Curr Opin Pharmacol. 2002;2(3):211–5.
Liu T, Yang L, Han X, Ding X, Li J, Yang J. Local sympathetic innervations modulate the lung innate immune responses. Sci Adv. 2020;6(20):eaay1497.
Acanfora D, Nolano M, Acanfora C, Colella C, Provitera V, Caporaso G, et al. Impaired vagal activity in long-COVID-19 patients. Viruses. 2022;14(5):1035.
Gu L, Zhou Y, Wang G, Deng H, Song X, He X, et al. Spatial learning and memory impaired after infection of non-neurotropic influenza virus in BALB/c male mice. Biochem Biophys Res Commun. 2021;540:29–36.
Moro J, Tomé D, Schmidely P, Demersay TC, Azzout-Marniche D. Histidine: a systematic review on metabolism and physiological effects in human and different animal species. Nutrients. 2020;12(5):1414.
Sheffield-Moore M, Dillon EL, Randolph KM, Casperson SL, White GR, Jennings K, et al. Isotopic decay of urinary or plasma 3-methylhistidine as a potential biomarker of pathologic skeletal muscle loss. J Cachexia Sarcopenia Muscle. 2014;5(1):19–25.
Albrecht J, Schousboe A. Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem Res. 2005;30(12):1615–21.
Oh SJ, Lee HJ, Jeong YJ, Nam KR, Kang KJ, Han SJ, et al. Evaluation of the neuroprotective effect of taurine in Alzheimer’s disease using functional molecular imaging. Sci Rep. 2020;10(1):15551.
Iwegbulem O, Wang J, Pfirrmann RW, Redmond HP. The role of taurine derivatives in the putative therapy of COVID-19-induced inflammation. Ir J Med Sci. 2022;191(1):485–6.
Jakaria M, Azam S, Haque ME, Jo SH, Uddin MS, Kim IS, et al. Taurine and its analogs in neurological disorders: focus on therapeutic potential and molecular mechanisms. Redox Biol. 2019;24:101223.
Heidari R, Jamshidzadeh A, Niknahad H, Mardani E, Ommati MM, Azarpira N, et al. Effect of taurine on chronic and acute liver injury: focus on blood and brain ammonia. Toxicol Rep. 2016;3:870–9.
Ghandforoush-Sattari M, Mashayekhi S. Evaluation of taurine as a biomarker of liver damage in paracetamol poisoning. Eur J Pharmacol. 2008;581(1–2):171–6.
de Oliveira DC, da Silva LF, Sartori T, Santos ACA, Rogero MM, Fock RA. Glutamine metabolism and its effects on immune response: molecular mechanism and gene expression. Nutrire. 2016;41(1):14.
Matsuyama T, Yoshinaga SK, Shibue K, Mak TW. Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19. Cell Death Differ. 2021;28(12):3199–213.
Hirabara SM, Gorjao R, Levada-Pires AC, Masi LN, Hatanaka E, Cury-Boaventura MF, et al. Host cell glutamine metabolism as a potential antiviral target. Clin Sci. 2021;135(2):305–25.
Chen J, Chen Y, Vail G, Chow H, Zhang Y, Louie L, et al. The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment. Mol Neurodegener. 2016;11(1):60.
Lee Y, Son H, Kim G, Kim S, Lee DH, Roh GS, et al. Glutamine deficiency in the prefrontal cortex increases depressive-like behaviours in male mice. J Psychiatry Neurosci. 2013;38(3):183–91.
Kumar A, Bachhawat AK. Pyroglutamic acid: throwing light on a lightly studied metabolite. Curr Sci. 2012;102(2):288–97.
Irani AZ, Borchert G, Craven B, Gibbons H. Flucloxacillin and paracetamol induced pyroglutamic acidosis. BMJ Case Rep. 2021;14(1):e237536.
Erra Díaz F, Dantas E, Geffner J. Unravelling the interplay between extracellular acidosis and immune cells. Mediators Inflamm. 2018;2018:1218297.
Zhao H, Cai Y, Yang Z, He D, Shen B. Acidosis leads to neurological disorders through overexciting cortical pyramidal neurons. Biochem Biophys Res Commun. 2011;415(2):224–8.
Wang Z, Bian L, Mo C, Shen H, Zhao LJ, Su KJ, et al. Quantification of aminobutyric acids and their clinical applications as biomarkers for osteoporosis. Commun Biol. 2020;3(1):39.
Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G. Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids. 2013;45(3):463–77.
Alves A, Bassot A, Bulteau AL, Pirola L, Morio B. Glycine metabolism and its alterations in obesity and metabolic diseases. Nutrients. 2019;11(6):1356.
Ayari A, Rosa-Calatrava M, Lancel S, Barthelemy J, Pizzorno A, Mayeuf-Louchart A, et al. Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues. Commun Biol. 2020;3(1):237.
Arenas YM, Cabrera-Pastor A, Juciute N, Mora-Navarro E, Felipo V. Blocking glycine receptors reduces neuroinflammation and restores neurotransmission in cerebellum through ADAM17-TNFR1-NF-κβ pathway. J Neuroinflammation. 2020;17(1):269.
Meléndez-Hevia E, de Paz-Lugo P, Sánchez G. Glycine can prevent and fight virus invasiveness by reinforcing the extracellular matrix. J Funct Foods. 2021;76:104318.
Dandare SU, Ezeonwumelu IJ, Shinkafi TS, Magaji UF, Adio AA, Ahmad K. L-alanine supplementation improves blood glucose level and biochemical indices in alloxan-induced diabetic rats. J Food Biochem. 2021;45(1):e13590.
Ron-Harel N, Ghergurovich JM, Notarangelo G, LaFleur MW, Tsubosaka Y, Sharpe AH, et al. T cell activation depends on extracellular alanine. Cell Rep. 2019;28(12):3011-21.e4.
Ohnuma T, Arai H. Significance of NMDA receptor-related glutamatergic amino acid levels in peripheral blood of patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(1):29–39.
Bourgin M, Durand S, Kroemer G. Diagnostic, prognostic and mechanistic biomarkers of COVID-19 Identified by mass spectrometric metabolomics. Metabolites. 2023;13(3):342.
Martí ILAA, Reith W. Arginine-dependent immune responses. Cell Mol Life Sci. 2021;78(13):5303–24.
Ikeda K, Yamasaki H, Suzuki Y, Koyama AH, Arakawa T. Novel strategy with acidic arginine solution for the treatment of influenza A virus infection. Exp Ther Med. 2010;1(2):251–6.
Wu J, Li G, Li L, Li D, Dong Z, Jiang P. Asparagine enhances LCK signalling to potentiate CD8+ T-cell activation and anti-tumour responses. Nat Cell Biol. 2021;23(1):75–86.
Pant A, Yang Z. Asparagine: an achilles heel of virus replication? ACS Infect Dis. 2020;6(9):2301–3.
Lee KE, Kang YS. Characteristics of (L)-citrulline transport through blood-brain barrier in the brain capillary endothelial cell line (TR-BBB cells). J Biomed Sci. 2017;24(1):28.
Wijnands KA, Castermans TM, Hommen MP, Meesters DM, Poeze M. Arginine and citrulline and the immune response in sepsis. Nutrients. 2015;7(3):1426–63.
Lange SM, McKell MC, Schmidt SM, Hossfeld AP, Chaturvedi V, Kinder JM, et al. l-Citrulline metabolism in mice augments CD4(+) T cell proliferation and cytokine production in vitro, and accumulation in the mycobacteria-infected lung. Front Immunol. 2017;8:1561.
Sikalidis AK. Amino acids and immune response: a role for cysteine, glutamine, phenylalanine, tryptophan and arginine in T-cell function and cancer? Pathol Oncol Res. 2015;21(1):9–17.
Dalangin R, Kim A, Campbell RE. The role of amino acids in neurotransmission and fluorescent tools for their detection. Int J Mol Sci. 2020;21(17):6197.
Wu G, Bazer FW, Burghardt RC, Johnson GA, Kim SW, Knabe DA, et al. Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids. 2011;40(4):1053–63.
Jongkees BJ, Hommel B, Kühn S, Colzato LS. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands—a review. J Psychiatr Res. 2015;70:50–7.
Krupa A, Kowalska I. The kynurenine pathway-new linkage between innate and adaptive immunity in autoimmune endocrinopathies. Int J Mol Sci. 2021;22(18):9879.
Davis I, Liu A. What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics? Expert Rev Neurother. 2015;15(7):719–21.
Gaelings L, Söderholm S, Bugai A, Fu Y, Nandania J, Schepens B, et al. Regulation of kynurenine biosynthesis during influenza virus infection. Febs J. 2017;284(2):222–36.
Wei GZ, Martin KA, Xing PY, Agrawal R, Whiley L, Wood TK, et al. Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor. Proc Natl Acad Sci USA. 2021;118(27):e2021091118.
Ji Y, Yin W, Liang Y, Sun L, Yin Y, Zhang W. Anti-inflammatory and anti-oxidative activity of indole-3-acetic acid involves induction of HO-1 and neutralization of free radicals in RAW264.7 cells. Int J Mol Sci. 2020;21(5):1579.
Chen Y, Tian P, Wang Z, Pan R, Shang K, Wang G, et al. Indole acetic acid exerts anti-depressive effects on an animal model of chronic mild stress. Nutrients. 2022;14(23):5019.
Ranjbar-Slamloo Y, Fazlali Z. Dopamine and noradrenaline in the brain; overlapping or dissociate functions? Front Mol Neurosci. 2019;12:334.
Attademo L, Bernardini F. Are dopamine and serotonin involved in COVID-19 pathophysiology? Eur J Psychiatry. 2021;35(1):62–3.
Landreau F, Galeano P, Caltana LR, Masciotra L, Chertcoff A, Pontoriero A, et al. Effects of two commonly found strains of influenza A virus on developing dopaminergic neurons, in relation to the pathophysiology of schizophrenia. PLoS ONE. 2012;7(12):e51068.
