Is There a Rendezvous for SARS-CoV-2 and Agmatine?

Nandkishor      Kotagale; Brijesh      Taksande; Nazma      Inamdar
Abstract

The catastrophe of the ongoing COVID-19 pandemic is caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). The respiratory system appears to be ground zero in the majority of the patients. However, many other organs can get infected by cytokines, chemokines and other mediators released in response to the presence of the virus. The neurotropism by the SARS-CoV-2 is established beyond doubt. In addition to non-specific symptoms, the symptoms specific to central and/or peripheral nervous system diseases as well as neuromuscular diseases have been observed in numerous clinical cases. These observations and the experiences with other coronavirus infections earlier and flu pandemics raise concerns not only about the neurological effects in active disease but also about the long-term effects generated by the infection, immune and inflammatory functions. The knowledge of biological actions of agmatine in the backdrop of physiological events instigated by invading SARS-CoV-2 and host’s response, especially in neural events, focuses on the possible overlaps of biomolecular pathways at a number of instances. This is not surprising since the factors stimulated during SARS-CoV-2 infection are the disease- generating neuroinflammatory components altered by agmatine. Hence, we hypothesize the possible beneficial role of agmatine in SARS-CoV-2 infection. Based on a narrative review of the literature, agmatine can be proposed as a plausible beneficial candidate for supporting treatment of SARS-CoV-2 infection and for addressing post-infection neurological complications.
Keywords: COVID-19, SARS-CoV-2, agmatine, neurotropism, neuroprotective, neuropsychiatry.
Graphical Abstract

[1] 
Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature  2020; 579(7798): 265-9.
[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508] 
[2] 
Zhu N, Zhang D, Wang W, et al. China Novel coronavirus investigating and research team. A novel coronavirus from patients with pneumonia in China. N Engl J Med  2020; 382(8): 727-33.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945] 
[3] 
Ksiazek TG, Erdman D, Goldsmith CS, et al. SARS working group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med  2003; 348(20): 1953-66.
[http://dx.doi.org/10.1056/NEJMoa030781] [PMID: 12690092] 
[4] 
Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol  2019; 17(3): 181-92.
[http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID: 30531947] 
[5] 
Zhong NS, Zheng BJ, Li YM, et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s republic of China, in February, 2003. Lancet  2003; 362(9393): 1353-8.
[http://dx.doi.org/10.1016/S0140-6736(03)14630-2] [PMID: 14585636] 
[6] 
de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol  2016; 14(8): 523-34.
[http://dx.doi.org/10.1038/nrmicro.2016.81] [PMID: 27344959] 
[7] 
 Available from:https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-emerging-variant.html (Accessed on 25 December 2020).
[8] 
Gandhi RT, Lynch JB, Del Rio C. Mild or moderate Covid-19. N Engl J Med  2020; 383(18): 1757-66.
[http://dx.doi.org/10.1056/NEJMcp2009249] [PMID: 32329974] 
[9] 
Ali Awan H, Najmuddin Diwan M, Aamir A, et al. SARS-CoV-2 and the brain: What do we know about the causality of 'cognitive COVID? J Clin Med  2021; 10(15): 3441.
[http://dx.doi.org/10.3390/jcm10153441] [PMID: 34362224] 
[10] 
Asadi-Pooya AA, Simani L. Central nervous system manifestations of COVID-19: A systematic review. Neurol Sci  2020; 413: 116832.
[http://dx.doi.org/10.1016/j.jns.2020.116832] [PMID: 32299017] 
[11] 
Li Y, Li M, Wang M, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol  2020; 5(3): 279-84.
[http://dx.doi.org/10.1136/svn-2020-000431] [PMID: 32616524] 
[12] 
Garner M, Reith W, Yilmaz U. COVID-19: neurologische Manifestationen - Update : Was wir bisher wissen. Radiologe  2021; 61(10): 902-908 [COVID-19: neurological manifestations-update:
What we know so far].
[http://dx.doi.org/10.1007/s00117-021-00907-2] [PMID: 34499188] 
[13] 
Sullivan BN, Fischer T. Age-Associated neurological complications of COVID-19: A systematic review and meta-analysis. Front Aging Neurosci  2021; 13: 653694.
[http://dx.doi.org/10.3389/fnagi.2021.653694] [PMID: 34408638] 
[14] 
Kushwaha S, Seth V, Bapat P, et al. Neurological associations of COVID-19-do we know enough: A tertiary care hospital based study. Front Neurol  2020; 11: 588879.
[http://dx.doi.org/10.3389/fneur.2020.588879] [PMID: 33329335] 
[15] 
Paniz-Mondolfi A, Bryce C, Grimes Z, et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol  2020; 92(7): 699-702.
[http://dx.doi.org/10.1002/jmv.25915] [PMID: 32314810] 
[16] 
Pouga L. Encephalitic syndrome and anosmia in COVID-19: Do these clinical presentations really reflect SARS-CoV-2 neurotropism? A theory based on the review of 25 COVID-19 cases. J Med Virol  2021; 93(1): 550-8.
[http://dx.doi.org/10.1002/jmv.26309] [PMID: 32672843] 
[17] 
Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol  2020; 16(11): 636-44.
[http://dx.doi.org/10.1038/s41582-020-0398-3] [PMID: 32839585] 
[18] 
Mao L, Jin H, Wang M, et al. Neurologic Manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol  2020; 77(6): 683-90.
[http://dx.doi.org/10.1001/jamaneurol.2020.1127] [PMID: 32275288] 
[19] 
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet  2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264] 
[20] 
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med  2020; 8(5): 475-81.
[http://dx.doi.org/10.1016/S2213-2600(20)30079-5] [PMID: 32105632] 
[21] 
Espiritu AI, Sy M, Anlacan V, Jamora R. Philippine CORONA Study Group Investigators. COVID-19 outcomes of 10,881 patients: retrospective study of neurological symptoms and associated manifestations (Philippine CORONA Study). J Neural Transm (Vienna, Austria: 1996)  2021; 1-17.
[http://dx.doi.org/10.1007/s00702-021-02400-5] 
[22] 
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet  2020; 395(10223): 507-13.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143] 
[23] 
Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of COVID-19 in the young. N Engl J Med  2020; 382(20): e60.
[http://dx.doi.org/10.1056/NEJMc2009787] [PMID: 32343504] 
[24] 
Sadeghmousavi S, Rezaei N. COVID-19 infection and stroke risk. Rev Neurosci  2020; 32(3): 341-9.
[http://dx.doi.org/10.1515/revneuro-2020-0066] [PMID: 33580645] 
[25] 
Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res  2020; 191: 145-7.
[http://dx.doi.org/10.1016/j.thromres.2020.04.013] [PMID: 32291094] 
[26] 
Meinhardt J, Radke J, Dittmayer C, et al. Olfactory transmucosal SARS-CoV-2 invasion as port of Central Nervous System entry in COVID-19 patients. 2020; bioRxiv  020.06.04.135012.
[http://dx.doi.org/10.1101/2020.06.04.135012] 
[27] 
Zulfiqar AA, Lorenzo-Villalba N, Hassler P, Andrès E. Immune thrombocytopenic purpura in a patient with COVID-19. N Engl J Med  2020; 382(18): e43.
[http://dx.doi.org/10.1056/NEJMc2010472] [PMID: 32294340] 
[28] 
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet  2020; 395(10234): 1417-8.
[http://dx.doi.org/10.1016/S0140-6736(20)30937-5] [PMID: 32325026] 
[29] 
Al Saiegh F, Ghosh R, Leibold A, et al. Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke. J Neurol Neurosurg Psychiatry  2020; 91(8): 846-8.
[http://dx.doi.org/10.1136/jnnp-2020-323522] [PMID: 32354770] 
[30] 
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: imaging features. Radiology  2020; 296(2): E119-20.
[http://dx.doi.org/10.1148/radiol.2020201187] [PMID: 32228363] 
[31] 
Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med  2020; 382(23): 2268-70.
[http://dx.doi.org/10.1056/NEJMc2008597] [PMID: 32294339] 
[32] 
Karimi N. SharifiRazavi, A.; Rouhani, N. Frequent convulsive seizures in an adult patient with COVID-9: A case report. Iran Red Crescent Med J  2020; 22: e02828.
[http://dx.doi.org/10.5812/ircmj.102828] 
[33] 
Elgamasy S, Kamel MG, Ghozy S, Khalil A, Morra ME, Islam SMS. First case of focal epilepsy associated with SARS-coronavirus-2. J Med Virol  2020; 92(10): 2238-42.
[http://dx.doi.org/10.1002/jmv.26113] [PMID: 32484990] 
[34] 
Lu L, Xiong W, Liu D, et al. New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study. Epilepsia  2020; 61(6): e49-53.
[http://dx.doi.org/10.1111/epi.16524] [PMID: 32304092] 
[35] 
Duong L, Xu P, Liu A. Meningoencephalitis without respiratory failure in a young female patient with COVID-19 infection in downtown Los Angeles, early April 2020. Brain Behav Immun  2020; 87: 33.
[http://dx.doi.org/10.1016/j.bbi.2020.04.024] [PMID: 32305574] 
[36] 
Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun  2020; 88: 945-6.
[http://dx.doi.org/10.1016/j.bbi.2020.04.017] [PMID: 32283294] 
[37] 
Sohal S, Mansur M. COVID-19 presenting with seizures. IDCases  2020; 20: e00782.
[http://dx.doi.org/10.1016/j.idcr.2020.e00782] [PMID: 32363146] 
[38] 
Zanin L, Saraceno G, Panciani PP, et al. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien)  2020; 162(7): 1491-1494  [Wien].
[http://dx.doi.org/10.1007/s00701-020-04374-x] [PMID: 32367205] 
[39] 
Zhang T, Rodricks MB, Hirsh E. COVID-19-associated acute disseminated encephalomyelitis: A case report 2020; medRxiv  2020.04.16.20068148.
[http://dx.doi.org/10.1101/2020.04.16.20068148] 
[40] 
Zhao K, Huang J, Dai D, Feng Y, Liu L, Nie S. Acute myelitis after SARS-CoV-2 infection: A case report. 2020; medRxiv  2020.03.16.20035105.
[http://dx.doi.org/10.1101/2020.03.16.20035105] 
[41] 
Canavero I, Ravaglia S, Valentino F, Micieli G. Guillain Barrè syndrome and myelitis associated with SARS-CoV-2 infection. Neurosci Lett  2021; 759: 136040.
[http://dx.doi.org/10.1016/j.neulet.2021.136040] [PMID: 34118307] 
[42] 
Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol  2020; 19(5): 383-4.
[http://dx.doi.org/10.1016/S1474-4422(20)30109-5] [PMID: 32246917] 
[43] 
Virani A, Rabold E, Hanson T, et al. Guillain-Barré Syndrome associated with SARS-CoV-2 infection. IDCases  2020; 20: e00771.
[http://dx.doi.org/10.1016/j.idcr.2020.e00771] [PMID: 32313807] 
[44] 
Sedaghat Z, Karimi N. Guillain Barre syndrome associated with COVID-19 infection: A case report. J Clin Neurosci  2020; 76: 233-5.
[http://dx.doi.org/10.1016/j.jocn.2020.04.062] [PMID: 32312628] 
[45] 
Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S, et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology  2020; 95(5): e601-5.
[http://dx.doi.org/10.1212/WNL.0000000000009619] [PMID: 32303650] 
[46] 
Jin M, Tong Q. Rhabdomyolysis as potential late complication associated with COVID-19. Emerg Infect Dis  2020; 26(7): 1618-20.
[http://dx.doi.org/10.3201/eid2607.200445] [PMID: 32197060] 
[47] 
Suwanwongse K, Shabarek N. Rhabdomyolysis as a presentation of 2019 novel coronavirus disease. Cureus  2020; 12(4): e7561.
[http://dx.doi.org/10.7759/cureus.7561] [PMID: 32382463] 
[48] 
Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet  2020; 395(10239): 1771-8.
[http://dx.doi.org/10.1016/S0140-6736(20)31103-X] [PMID: 32410760] 
[49] 
Lanese N. Woman with COVID- 9 developed a rare brain condition. doctors suspect a link. Available via DIALOG. 2020. Available from: https://www.livescience.com/woman-with-covid 9- coronavirus-had-rare-braindisease.html
[50] 
Dinkin M, Gao V, Kahan J, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology  2020; 95(5): 221-3.
[http://dx.doi.org/10.1212/WNL.0000000000009700] [PMID: 32358218] 
[51] 
Sriwijitalai W, Wiwanitkit V. Hearing loss and COVID-19: A note. Am J Otolaryngol  2020; 41(3): 102473.
[http://dx.doi.org/10.1016/j.amjoto.2020.102473] [PMID: 32276732] 
[52] 
Varatharaj A, Thomas N, Ellul MA, et al. CoroNerve Study Group. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry  2020; 7(10): 875-82.
[http://dx.doi.org/10.1016/S2215-0366(20)30287-X] [PMID: 32593341] 
[53] 
Zhou L, Zhang M, Wang J, Gao J. SARS-CoV-2: Underestimated damage to nervous system. Travel Med Infect Dis  2020; 36: 101642.
[http://dx.doi.org/10.1016/j.tmaid.2020.101642] [PMID: 32220634] 
[54] 
Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis  2020; 94: 55-8.
[http://dx.doi.org/10.1016/j.ijid.2020.03.062] [PMID: 32251791] 
[55] 
Solomon IH, Normandin E, Bhattacharyya S, et al. Neuropathological features of Covid-19. N Engl J Med  2020; 383(10): 989-92.
[http://dx.doi.org/10.1056/NEJMc2019373] [PMID: 32530583] 
[56] 
Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med  2020; 383(6): 590-2.
[http://dx.doi.org/10.1056/NEJMc2011400] [PMID: 32402155] 
[57] 
Cantuti-Castelvetri L, Ojha R, Pedro LD, et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system bioRxiv 2020.
[http://dx.doi.org/10.1101/2020.06.07.137802] 
[58] 
Bulfamante G, Chiumello D, Canevini MP, et al. First ultrastructural autoptic findings of SARS -Cov-2 in olfactory pathways and brainstem. Minerva Anestesiol  2020; 86(6): 678-9.
[http://dx.doi.org/10.23736/S0375-9393.20.14772-2] [PMID: 32401000] 
[59] 
Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol  2008; 82(15): 7264-75.
[http://dx.doi.org/10.1128/JVI.00737-08] [PMID: 18495771] 
[60] 
Baig AM, Sanders EC. Potential neuroinvasive pathways of SARS-CoV-2: Deciphering the spectrum of neurological deficit seen in coronavirus disease-2019 (COVID-19). J Med Virol  2020; 92(10): 1845-57.
[http://dx.doi.org/10.1002/jmv.26105] [PMID: 32492193] 
[61] 
Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature  2015; 523(7560): 337-41.
[http://dx.doi.org/10.1038/nature14432] [PMID: 26030524] 
[62] 
Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol  2020; 92(6): 552-5.
[http://dx.doi.org/10.1002/jmv.25728] [PMID: 32104915] 
[63] 
Wong SH, Lui RN, Sung JJ. Covid-19 and the digestive system. J Gastroenterol Hepatol  2020; 35(5): 744-8.
[http://dx.doi.org/10.1111/jgh.15047] [PMID: 32215956] 
[64] 
Bolay H, Gül A, Baykan B. COVID-19 is a real headache! Headache  2020; 60(7): 1415-21.
[http://dx.doi.org/10.1111/head.13856] [PMID: 32412101] 
[65] 
Brann DH, Tsukahara T, Weinreb C, Logan DW, Datta SR. Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients 2020; bioRxiv  2020.03.25.009084.
[http://dx.doi.org/10.1101/2020.03.25.009084] 
[66] 
Ueha R, Kondo K, Kagoya R, Shichino S, Ueha S, Yamasoba T. Background mechanisms of olfactory dysfunction in COVID-19: Expression of ACE2, TMPRSS2, and furin in the nose and olfactory bulb in human and mice 2020; bioRxiv  020.05.15.097352.
[http://dx.doi.org/10.1101/2020.05.15.097352] 
[67] 
Llorens S, Nava E, Muñoz-López M, Sánchez-Larsen Á, Segura T. Neurological symptoms of COVID-19: The zonulin hypothesis. Front Immunol  2021; 12: 665300.
[http://dx.doi.org/10.3389/fimmu.2021.665300] [PMID: 33981312] 
[68] 
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell  2020; 181(2): 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651] 
[69] 
Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun  2020; 11(1): 1620.
[http://dx.doi.org/10.1038/s41467-020-15562-9] [PMID: 32221306] 
[70] 
Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci  2020; 12(1): 8.
[http://dx.doi.org/10.1038/s41368-020-0074-x] [PMID: 32094336] 
[71] 
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol  2004; 203(2): 631-7.
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377] 
[72] 
Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell  2020; 181(2): 281-292.e6.
[http://dx.doi.org/10.1016/j.cell.2020.02.058] [PMID: 32155444] 
[73] 
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. J Virol  2020; 94(7): e00127-20.
[http://dx.doi.org/10.1128/JVI.00127-20] [PMID: 31996437] 
[74] 
Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science  2020; 367(6483): 1260-3.
[http://dx.doi.org/10.1126/science.abb2507] [PMID: 32075877] 
[75] 
Wang Q, Zhang Y, Wu L, et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell  2020; 181(4): 894-904.
[http://dx.doi.org/10.1016/j.cell.2020.03.045] 
[76] 
Shang J, Ye G, Shi K, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature  2020; 581(7807): 221-4.
[http://dx.doi.org/10.1038/s41586-020-2179-y] [PMID: 32225175] 
[77] 
Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol  2005; 5(12): 917-27.
[http://dx.doi.org/10.1038/nri1732] [PMID: 16322745] 
[78] 
Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun  2020; 526(1): 135-40.
[http://dx.doi.org/10.1016/j.bbrc.2020.03.044] [PMID: 32199615] 
[79] 
Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spike-host cell receptor GRP78 binding site prediction. J Infect  2020; 80(5): 554-62.
[http://dx.doi.org/10.1016/j.jinf.2020.02.026] [PMID: 32169481] 
[80] 
Wang K, Chen W, Zhou Y-S, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein 2020; bioRxiv  2020.03.14.988345.
[http://dx.doi.org/10.1101/2020.03.14.988345] 
[81] 
Shiers S, Ray PR, Wangzhou A, et al. ACE2 expression in human dorsal root ganglion sensory neurons: Implications for SARS-CoV-2 virus-induced neurological effects 2020; bioRxiv  2020: 2020.2005.2028.122374.
[http://dx.doi.org/10.1101/2020.05.28.122374] 
[82] 
Singh KK, Chaubey G, Chen JY, Suravajhala P. Decoding SARS- CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis. Am J Physiol Cell Physiol  2020; 319(2): C258-67.
[http://dx.doi.org/10.1152/ajpcell.00224.2020] [PMID: 32510973] 
[83] 
Daly JL, Simonetti B, Antón-Plágaro C, et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection 2020; bioRxiv  2020.06.05.134114.
[http://dx.doi.org/10.1101/2020.06.05.134114] 
[84] 
Davies J, Randeva HS, Chatha K, et al. Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19. Mol Med Rep  2020; 22(5): 4221-6.
[http://dx.doi.org/10.3892/mmr.2020.11510] [PMID: 33000221] 
[85] 
Yesilkaya UH, Balcioglu YH, Sahin S. Reissuing the sigma receptors for SARS-CoV-2. J Clin Neurosci  2020; 80: 72-3.
[http://dx.doi.org/10.1016/j.jocn.2020.08.014] [PMID: 33099370] 
[86] 
Piletz JE, Aricioglu F, Cheng JT, et al. Agmatine: clinical applications after 100 years in translation. Drug Discov Today  2013; 18(17-18): 880-93.
[http://dx.doi.org/10.1016/j.drudis.2013.05.017] [PMID: 23769988] 
[87] 
Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic alterations due to respiratory virus infections. Front Cell Neurosci  2018; 12: 386.
[http://dx.doi.org/10.3389/fncel.2018.00386] [PMID: 30416428] 
[88] 
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH across speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet  2020; 395(10229): 1033-4.
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578] 
[89] 
Savarin C, Bergmann CC. Viral-induced suppression of self-reactive T cells: Lessons from neurotropic coronavirus-induced demyelination. J Neuroimmunol  2017; 308: 12-6.
[http://dx.doi.org/10.1016/j.jneuroim.2017.01.003] [PMID: 28108025] 
[90] 
Kanberg N, Ashton NJ, Andersson LM, et al. Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology  2020; 95(12): e1754-9.
[http://dx.doi.org/10.1212/WNL.0000000000010111] [PMID: 32546655] 
[91] 
Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, et al. The SARS- CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in vitro models of the human blood-brain barrier. 2020.bioRxiv 
[http://dx.doi.org/10.1101/2020.06.15.150912] 
[92] 
Sasannejad C, Ely EW, Lahiri S. Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms. Crit Care  2019; 23(1): 352.
[http://dx.doi.org/10.1186/s13054-019-2626-z] [PMID: 31718695] 
[93] 
Kotagale NR, Taksande BG, Inamdar NN. Neuroprotective offerings by agmatine. Neurotoxicology  2019; 73: 228-45.
[http://dx.doi.org/10.1016/j.neuro.2019.05.001] [PMID: 31063707] 
[94] 
Yang XC, Reis DJ. Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther  1999; 288(2): 544-9.
[PMID: 9918557] 
[95] 
Wang WP, Iyo AH, Miguel-Hidalgo J, Regunathan S, Zhu MY. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons. Brain Res  2006; 1084(1): 210-6.
[http://dx.doi.org/10.1016/j.brainres.2006.02.024] [PMID: 16546145] 
[96] 
Li F, Wu N, Su RB, et al. Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein. J Cell Biochem  2006; 98(6): 1615-28.
[http://dx.doi.org/10.1002/jcb.20806] [PMID: 16598778] 
[97] 
Wei H, Jyväsjärvi E, Niissalo S, et al. The influence of chemical sympathectomy on pain responsivity and alpha 2-adrenergic antinociception in neuropathic animals. Neuroscience  2002; 114(3): 655-68.
[http://dx.doi.org/10.1016/S0306-4522(02)00328-7] [PMID: 12220567] 
[98] 
Dixit MP, Upadhya MA, Taksande BG, Raut P, Umekar MJ, Kotagale NR. Neuroprotective effect of agmatine in mouse spinal cord injury model: modulation by imidazoline receptors. J Nat Sci Biol Med  2018; 9(2): 115-20.
[http://dx.doi.org/10.4103/jnsbm.JNSBM_239_17] 
[99] 
Qiu WW, Zheng RY. Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine. Neurosci Bull  2006; 22(3): 187-91.
[PMID: 17704848] 
[100] 
Shepherd RM, Hashmi MN, Kane C, Squires PE, Dunne MJ. Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus-response coupling of insulin release. Br J Pharmacol  1996; 119(5): 911-6.
[http://dx.doi.org/10.1111/j.1476-5381.1996.tb15759.x] [PMID: 8922740] 
[101] 
Santhanam AV, Viswanathan S, Dikshit M. Activation of protein kinase B/Akt and endothelial nitric oxide synthase mediates agmatine-induced endothelium-dependent relaxation. Eur J Pharmacol  2007; 572(2-3): 189-96.
[http://dx.doi.org/10.1016/j.ejphar.2007.06.031] [PMID: 17640632] 
[102] 
Pfeiffer B, Sarrazin W, Weitzel G. InsulinähnlicheEffekte von Agmatin derivaten in vitro and in vivo Insulin-like effects of agmatine derivatives in vitro and in vivo. Hoppe Seylers Z Physiol Chem  1981; 362(2): 1331-7.
[http://dx.doi.org/10.1515/bchm2.1981.362.2.1331] [PMID: 7030911] 
[103] 
Sener A, Lebrun P, Blachier F, Malaisse WJ. Stimulus-secretion coupling of arginine-induced insulin release. Insulinotropic action of agmatine. Biochem Pharmacol  1989; 38(2): 327-30.
[http://dx.doi.org/10.1016/0006-2952(89)90044-0] [PMID: 2643944] 
[104] 
Auguet M, Viossat I, Marin JG, Chabrier PE. Selective inhibition of inducible nitric oxide synthase by agmatine. Jpn J Pharmacol  1995; 69(3): 285-7.
[http://dx.doi.org/10.1254/jjp.69.285] [PMID: 8699639] 
[105] 
Galea E, Regunathan S, Eliopoulos V, Feinstein DL, Reis DJ. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J  1996; 316(Pt 1): 247-9.
[http://dx.doi.org/10.1042/bj3160247] [PMID: 8645212] 
[106] 
Abe K, Abe Y, Saito H. Agmatine suppresses nitric oxide production in microglia. Brain Res  2000; 872(1-2): 141-8.
[http://dx.doi.org/10.1016/S0006-8993(00)02517-8] [PMID: 10924686] 
[107] 
Dejanovic B, Vukovic-Dejanovic V, Ninkovic M, et al. Effects of agmatine on chlorpromazine-induced neuronal injury in rat. Acta Vet Brno  2018; 87: 145-53.
[http://dx.doi.org/10.2754/avb201887020145] 
[108] 
Chai J, Luo L, Hou F, et al. Agmatine reduces lipopolysaccharide- mediated oxidant response via activating PI3K/Akt pathway and up-Regulating Nrf2 and HO-1 expression in macrophages. PLoS One  2016; 11(9): e0163634.
[http://dx.doi.org/10.1371/journal.pone.0163634] [PMID: 27685463] 
[109] 
Takahashi K, Greenberg JH, Jackson P, Maclin K, Zhang J. Neuroprotective effects of inhibiting poly(ADP-ribose) synthetase on focal cerebral ischemia in rats. J Cereb Blood Flow Metab  1997; 17(11): 1137-42.
[http://dx.doi.org/10.1097/00004647-199711000-00001] [PMID: 9390644] 
[110] 
Laing S, Unger M, Koch-Nolte F, Haag F. ADP-ribosylation of arginine. Amino Acids  2011; 41(2): 257-69.
[http://dx.doi.org/10.1007/s00726-010-0676-2] [PMID: 20652610] 
[111] 
Zhu MY, Wang WP, Cai ZW, Regunathan S, Ordway G. Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain. Eur J Neurosci  2008; 27(6): 1320-32.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06104.x] [PMID: 18364017] 
[112] 
Zhu MY, Wang WP, Huang J, Feng YZ, Regunathan S, Bissette G. Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. Neurochem Int  2008; 53(6-8): 346-54.
[http://dx.doi.org/10.1016/j.neuint.2008.09.001] [PMID: 18832001] 
[113] 
Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol  2020; 20(6): 355-62.
[http://dx.doi.org/10.1038/s41577-020-0331-4] [PMID: 32376901] 
[114] 
Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest  2020; 130(5): 2620-9.
[http://dx.doi.org/10.1172/JCI137244] [PMID: 32217835] 
[115] 
Liu T, Zhang J, Yang Y, et al. The role of interleukin-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med  2020; 12(7): e12421.
[http://dx.doi.org/10.15252/emmm.202012421] [PMID: 32428990] 
[116] 
Chen X, Zhao B, Qu Y, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin Infect Dis  2020; 71(8): 1937-42.
[http://dx.doi.org/10.1093/cid/ciaa449] [PMID: 32301997] 
[117] 
Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med  2020; 46(5): 846-8.
[http://dx.doi.org/10.1007/s00134-020-05991-x] [PMID: 32125452] 
[118] 
Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol  2020; 5(7): 802-10.
[http://dx.doi.org/10.1001/jamacardio.2020.0950] [PMID: 32211816] 
[119] 
Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog Cardiovasc Dis  2020; 63(3): 390-1.
[http://dx.doi.org/10.1016/j.pcad.2020.03.001] [PMID: 32169400] 
[120] 
Taxbro K, Kahlow H, Wulcan H, Fornarve A. Rhabdomyolysis and acute kidney injury in severe COVID-19 infection. BMJ Case Rep  2020; 13(9): e237616.
[http://dx.doi.org/10.1136/bcr-2020-237616] [PMID: 32878841] 
[121] 
Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med  2020; 58(7): 1116-20.
[http://dx.doi.org/10.1515/cclm-2020-0188] [PMID: 32172226] 
[122] 
Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol  2020; 127: 104362.
[http://dx.doi.org/10.1016/j.jcv.2020.104362] [PMID: 32305883] 
[123] 
Zhao S, Wang B, Yuan H, Xiao D. Determination of agmatine in biological samples by capillary electrophoresis with optical fiber light-emitting-diode-induced fluorescence detection. J Chromatogr A  2006; 1123(1): 138-41.
[http://dx.doi.org/10.1016/j.chroma.2006.05.038] [PMID: 16820162] 
[124] 
Lortie MJ, Ishizuka S, Schwartz D, Blantz RC. Bioactive products of arginine in sepsis: tissue and plasma composition after LPS and iNOS blockade. Am J Physiol Cell Physiol  2000; 278(6): C1191-9.
[http://dx.doi.org/10.1152/ajpcell.2000.278.6.C1191] [PMID: 10837347] 
[125] 
Li X, Zhu J, Tian L, et al. Agmatine protects against the progression of sepsis through the imidazoline I2 receptor-ribosomal S6 kinase 2-Nuclear factor-κBsignaling pathway. Crit Care Med  2020; 48(1): e40-7.
[http://dx.doi.org/10.1097/CCM.0000000000004065] [PMID: 31634234] 
[126] 
Sahin C, Albayrak O, Akdeniz TF, Akbulut Z, Yanikkaya Demirel G, Aricioglu F. Agmatine reverses sub-chronic stress induced Nod-like receptor protein 3 (NLRP3) activation and cytokine response in rats. Basic Clin Pharmacol Toxicol  2016; 119(4): 367-75.
[http://dx.doi.org/10.1111/bcpt.12604] [PMID: 27061450] 
[127] 
Nicol GE, Karp JF, Reiersen AM, Zorumski CF, Lenze EJ. What were you before the war?" repurposing psychiatry during the covid-19 pandemic. J Clin Psychiatry  2020; 81(3)
[http://dx.doi.org/10.4088/JCP.20com13373] 
[128] 
Ishima T, Fujita Y, Hashimoto K. Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells. Eur J Pharmacol  2014; 727: 167-73.
[http://dx.doi.org/10.1016/j.ejphar.2014.01.064] [PMID: 24508523] 
[129] 
Hashimoto K. Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication. J Pharmacol Sci  2015; 127(1): 6-9.
[http://dx.doi.org/10.1016/j.jphs.2014.11.010] [PMID: 25704012] 
[130] 
Rosen DA, Seki SM, Fernández-Castañeda A, et al. Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Sci Transl Med  2019; 11(478): eaau5266.
[http://dx.doi.org/10.1126/scitranslmed.aau5266] [PMID: 30728287] 
[131] 
Taksande BG, Kotagale NR, Tripathi SJ, Ugale RR, Chopde CT. Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine. Neuropharmacology  2009; 57(4): 415-24.
[http://dx.doi.org/10.1016/j.neuropharm.2009.06.035] [PMID: 19589348] 
[132] 
Kotagale NR, Shirbhate SH, Shukla P, Ugale RR. Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by hippocampal sigma receptors. Eur J Pharmacol  2013; 714(1-3): 424-31.
[http://dx.doi.org/10.1016/j.ejphar.2013.07.005] [PMID: 23872381] 
[133] 
Regunathan S, Piletz JE. Regulation of inducible nitric oxide synthase and agmatine synthesis in macrophages and astrocytes. Ann N Y Acad Sci  2003; 1009: 20-9.
[http://dx.doi.org/10.1196/annals.1304.002] [PMID: 15028566] 
[134] 
Sastre M, Galea E, Feinstein D, Reis DJ, Regunathan S. Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines. Biochem J  1998; 330(Pt 3): 1405-9.
[http://dx.doi.org/10.1042/bj3301405] [PMID: 9494113] 
[135] 
Kim JH, Kim JY, Mun CH, Suh M, Lee JE. Agmatine modulates the phenotype of macrophage acute phase after spinal cord injury in rats. Exp Neurobiol  2017; 26(5): 278-86.
[http://dx.doi.org/10.5607/en.2017.26.5.278] [PMID: 29093636] 
[136] 
Satriano J, Schwartz D, Ishizuka S, et al. Suppression of inducible nitric oxide generation by agmatine aldehyde: beneficial effects in sepsis. J Cell Physiol  2001; 188(3): 313-20.
[http://dx.doi.org/10.1002/jcp.1119] [PMID: 11473357] 
[137] 
Satriano J. Agmatine: at the crossroads of the arginine pathways. Ann N Y Acad Sci  2003; 1009: 34-43.
[http://dx.doi.org/10.1196/annals.1304.004] [PMID: 15028568] 
[138] 
Freitas AE, Egea J, Buendía I, et al. Agmatine induces Nrf2 and protects against corticosterone effects in hippocampal neuronal cell line. Mol Neurobiol  2015; 51(3): 1504-19.
[http://dx.doi.org/10.1007/s12035-014-8827-1] [PMID: 25084759] 
[139] 
Freitas AE, Bettio LE, Neis VB, et al. Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice. Prog Neuropsychopharmacol Biol Psychiatry  2014; 50: 143-50.
[http://dx.doi.org/10.1016/j.pnpbp.2013.12.012] [PMID: 24370459] 
[140] 
Bila I, Dzydzan O, Brodyak I, Sybirna N. Agmatine prevents oxidative-nitrative stress in blood leukocytes under streptozotocin-induced diabetes mellitus. Open Life Sci  2019; 14: 299-310.
[http://dx.doi.org/10.1515/biol-2019-0033] [PMID: 33817163] 
[141] 
Stevanovic I, Ninkovic M, Stojanovic I, Ljubisavljevic S, Stojnev S, Bokonjic D. Beneficial effect of agmatine in the acute phase of experimental autoimmune encephalomyelitis in iNOS-/- knockout mice. Chem Biol Interact  2013; 206(2): 309-18.
[http://dx.doi.org/10.1016/j.cbi.2013.09.006] [PMID: 24070732] 
[142] 
Li X, Liu Z, Jin H, et al. Agmatine protects against zymosan-induced acute lung injury in mice by inhibiting NF-κB-mediated inflammatory response. BioMed Res Int  2014; 2014: 583736.
[http://dx.doi.org/10.1155/2014/583736] [PMID: 25243152] 
[143] 
Liu G, Mei H, Chen M, et al. Protective effect of agmatine against hyperoxia-induced acute lung injury via regulating lncRNA gadd7. Biochem Biophys Res Commun  2019; 516(1): 68-74.
[http://dx.doi.org/10.1016/j.bbrc.2019.04.164] [PMID: 31196629] 
[144] 
Moon SU, Kwon KH, Kim JH, et al. Recombinant hexahistidine arginine decarboxylase (hisADC) induced endogenous agmatine synthesis during stress. Mol Cell Biochem  2010; 345(1-2): 53-60.
[http://dx.doi.org/10.1007/s11010-010-0559-6] [PMID: 20730478] 
[145] 
Demady DR, Jianmongkol S, Vuletich JL, Bender AT, Osawa Y. Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Mol Pharmacol  2001; 59(1): 24-9.
[http://dx.doi.org/10.1124/mol.59.1.24] [PMID: 11125020] 
[146] 
Morrissey JJ, Klahr S. Effects of agmatine, an active metabolite of arginine metabolism, on the kidney. Nephrol Dial Transplant  1996; 11(7): 1217-9.
[http://dx.doi.org/10.1093/ndt/11.7.1217] [PMID: 8672006] 
[147] 
Schwartz D, Peterson OW, Mendonca M, Satriano J, Lortie M, Blantz RC. Agmatine affects glomerular filtration via a nitric oxide synthase-dependent mechanism. Am J Physiol  1997; 272(5 Pt 2): F597-601.
[http://dx.doi.org/10.1152/ajprenal.1997.272.5.F597] [PMID: 9176369] 
[148] 
Ten Broeke R, De Crom R, Van Haperen R, et al. Overexpression of endothelial nitric oxide synthase suppresses features of allergic asthma in mice. Respir Res  2006; 7(1): 58.
[http://dx.doi.org/10.1186/1465-9921-7-58] [PMID: 16597326] 
[149] 
Gilad G M, Salame K, Rabey J M, Gilad V H. Agmatine treatment is neuroprotective in rodent brain injury models. Life Sci  1996; 58(2): 41-6.
[http://dx.doi.org/10.1016/0024-3205(95)02274-0] 
[150] 
Gilad GM, Gilad VH. Accelerated functional recovery and neuroprotection by agmatine after spinal cord ischemia in rats. Neurosci Lett  2000; 296(2-3): 97-100.
[http://dx.doi.org/10.1016/S0304-3940(00)01625-6] [PMID: 11108990] 
[151] 
Kim DJ, Kim DI, Lee SK, et al. Protective effect of agmatine on a reperfusion model after transient cerebral ischemia: Temporal evolution on perfusion MR imaging and histopathologic findings. AJNR Am J Neuroradiol  2006; 27(4): 780-5.
[PMID: 16611764] 
[152] 
Kim JH, Yenari MA, Giffard RG, Cho SW, Park KA, Lee JE. Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia- like injury. Exp Neurol  2004; 189(1): 122-30.
[http://dx.doi.org/10.1016/j.expneurol.2004.05.029] [PMID: 15296842] 
[153] 
Hong S, Lee JE, Kim CY, Seong GJ. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line. BMC Neurosci  2007; 8: 81.
[http://dx.doi.org/10.1186/1471-2202-8-81] [PMID: 17908330] 
[154] 
Feng Y, Piletz JE, Leblanc MH. Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res  2002; 52(4): 606-11.
[http://dx.doi.org/10.1203/00006450-200210000-00023] [PMID: 12357058] 
[155] 
Kim JH, Lee YW, Park KA, Lee WT, Lee JE. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia. J Cereb Blood Flow Metab  2010; 30(5): 943-9.
[http://dx.doi.org/10.1038/jcbfm.2009.260] [PMID: 20029450] 
[156] 
Lee WT, Hong S, Yoon SH, et al. Neuroprotective effects of agmatine on oxygen-glucose deprived primary-cultured astrocytes and nuclear translocation of nuclear factor-kappa B. Brain Res  2009; 1281: 64-70.
[http://dx.doi.org/10.1016/j.brainres.2009.05.046] [PMID: 19465011] 
[157] 
Mun CH, Lee WT, Park KA, Lee JE. Agmatine reduced the expressions of nitric oxide synthase and peroxynitrite formation in rat cerebral cortex after transient global cerebral ischemia. Neural Regen Res  2010; 5(23): 1773-81.
[http://dx.doi.org/10.3969/j.issn.1673-5374.2010.23.002] 
[158] 
Fairbanks C, Kaminski L, Nguyen H. Pre-treatment with antisera raised against agmatine sensitizes mice to plasticity-mediated events. Soc Neurosci  2001; 27: 465.
[159] 
Hong JS, Jeon H, Jeong HS, et al. Quantification of agmatine by HPLC method in mouse middle cerebral artery occlusion model. Korean J Anat  2003; 36(4): 257-64.
[160] 
Kim JH, Kim JY, Jung JY, et al. Endogenous agmatine induced by ischemic preconditioning regulates ischemic tolerance following cerebral ischemia. Exp Neurobiol  2017; 26(6): 380-9.
[http://dx.doi.org/10.5607/en.2017.26.6.380] [PMID: 29302205] 
[161] 
Cigdem B, Bolayir A, Celik VK, et al. The Role of reduced polyamine synthesis in ischemic stroke. Neurochem J  2020; 4(2): 243-50.
[http://dx.doi.org/10.1134/S1819712420020038] 
[162] 
Iadecola C, Zhang F, Xu S, Casey R, Ross ME. Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J Cereb Blood Flow Metab  1995; 15(3): 378-84.
[http://dx.doi.org/10.1038/jcbfm.1995.47] [PMID: 7536197] 
[163] 
Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci  1997; 20(3): 132-9.
[http://dx.doi.org/10.1016/S0166-2236(96)10074-6] [PMID: 9061868] 
[164] 
Mun CH, Lee WT, Park KA, Lee JE. Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain. Anat Cell Biol  2010; 43(3): 230-40.
[http://dx.doi.org/10.5115/acb.2010.43.3.230] [PMID: 21212863] 
[165] 
Ahn SK, Hong S, Park YM, Lee WT, Park KA, Lee JE. Effects of agmatine on hypoxic microglia and activity of nitric oxide synthase. Brain Res  2011; 1373: 48-54.
[http://dx.doi.org/10.1016/j.brainres.2010.12.002] [PMID: 21145312] 
[166] 
Ahn SK, Hong S, Park YM, et al. Protective effects of agmatine on lipopolysaccharide-injured microglia and inducible nitric oxide synthase activity. Life Sci  2012; 91(25-26): 1345-50.
[http://dx.doi.org/10.1016/j.lfs.2012.10.010] [PMID: 23123442] 
[167] 
Mun CH, Kim JH, Park KA, Lee WT, Baik JH, Lee JE. Agmatine attenuates nitric oxide synthesis and protects ER-structure from global cerebral ischemia in rat hippocampus. Korean J Anat  2009; 42(3): 149-60.
[168] 
Mun CH, Lee WT, Park KA, Lee JE. Agmatine reduces nitric oxide synthase expression and peroxynitrite formation in the cerebral cortex in a rat model of transient global cerebral ischemia. Neural Regen Res  2010; 5(23): 1773-81.
[http://dx.doi.org/10.3969/j.issn.1673-5374.2010.23.002] 
[169] 
Ouyang YB, Giffard RG. ER-mitochondria crosstalk during cerebral ischemia: Molecular chaperones and ER-mitochondrial calcium transfer. Int J Cell Biol  2012; 2012: 493934.
[http://dx.doi.org/10.1155/2012/493934] [PMID: 22577383] 
[170] 
Nakka VP, Gusain A, Raghubir R. Endoplasmic reticulum stress plays critical role in brain damage after cerebral ischemia/reperfusion in rats. Neurotox Res  2010; 17(2): 189-202.
[http://dx.doi.org/10.1007/s12640-009-9110-5] [PMID: 19763736] 
[171] 
Huang YC, Tzeng WS, Wang CC, et al. Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation. Magn Reson Imaging  2013; 31(7): 1174-81.
[http://dx.doi.org/10.1016/j.mri.2013.03.026] [PMID: 23642800] 
[172] 
Wang CC, Chio CC, Chang CH, Kuo JR, Chang CP. Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia. BMC Pharmacol  2010; 10: 11.
[http://dx.doi.org/10.1186/1471-2210-10-11] [PMID: 20815926] 
[173] 
Kim JY, Lee YW, Kim JH, Lee WT, Park KA, Lee JE. Agmatine attenuates brain edema and apoptotic cell death after traumatic brain injury. J Korean Med Sci  2015; 30(7): 943-52.
[http://dx.doi.org/10.3346/jkms.2015.30.7.943] [PMID: 26130959] 
[174] 
Ahn SS, Kim SH, Lee JE, et al. Effects of agmatine on blood-brain barrier stabilization assessed by permeability MRI in a rat model of transient cerebral ischemia. AJNR Am J Neuroradiol  2015; 36(2): 283-8.
[http://dx.doi.org/10.3174/ajnr.A4113] [PMID: 25273536] 
[175] 
Moss J, Yost DA, Stanley SJ. Amino acid-specific ADP-ribosylation. J Biol Chem  1983; 258(10): 6466-70.
[http://dx.doi.org/10.1016/S0021-9258(18)32434-7] [PMID: 6304041] 
[176] 
Hong S, Park K, Kim CY, Seong GJ. Agmatine inhibits hypoxia-induced TNF-alpha release from cultured retinal ganglion cells. Biocell  2008; 32(2): 201-5.
[http://dx.doi.org/10.32604/biocell.2008.32.201] [PMID: 18825914] 
[177] 
Uranchimeg D, Kim JH, Kim JY, et al. Recovered changes in the spleen by agmatine treatment after transient cerebral ischemia. Anat Cell Biol  2010; 43(1): 44-53.
[http://dx.doi.org/10.5115/acb.2010.43.1.44] [PMID: 21190004] 
[178] 
Selakovic V, Arsenijevic L, Jovanovic M, et al. Functional and pharmacological analysis of agmatine administration in different cerebral ischemia animal models. Brain Res Bull  2019; 146: 201-12.
[http://dx.doi.org/10.1016/j.brainresbull.2019.01.005] [PMID: 30641119] 
[179] 
Houtman JJ, Fleming JO. Pathogenesis of mouse hepatitis virus-induced demyelination. J Neurovirol  1996; 2(6): 361-76.
[http://dx.doi.org/10.3109/13550289609146902] [PMID: 8972418] 
[180] 
Shindler KS, Kenyon LC, Dutt M, Hingley ST, Das Sarma J. Experimental optic neuritis induced by a demyelinating strain of mouse hepatitis virus. J Virol  2008; 82(17): 8882-6.
[http://dx.doi.org/10.1128/JVI.00920-08] [PMID: 18579591] 
[181] 
Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med  2020; 382(17): e38.
[http://dx.doi.org/10.1056/NEJMc2007575] [PMID: 32268022] 
[182] 
Rege S, Mackworth-Young C. Antiphospholipid antibodies as biomarkers in psychiatry: review of psychiatric manifestations in antiphospholipid syndrome. Transl Dev Psychiatry  2015; 3(1): 25452.
[http://dx.doi.org/10.3402/tdp.v3.25452] 
[183] 
Li YF, Chen HX, Liu Y, Zhang Y-Z, Liu Y-Q, Li J. Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice. Acta Pharmacol Sin  2006; 27(11): 1395-400.
[http://dx.doi.org/10.1111/j.1745-7254.2006.00429.x] [PMID: 17049113] 
[184] 
Kuo JR, Lo CJ, Chang CP, Lin KC, Lin MT, Chio CC. Agmatine-promoted angiogenesis, neurogenesis, and inhibition of gliosis-reduced traumatic brain injury in rats. J Trauma  2011; 71(4): E87-93.
[http://dx.doi.org/10.1097/TA.0b013e31820932e2] [PMID: 21427621] 
[185] 
Song HW, Kumar BK, Kim SH, et al. Agmatine enhances neurogenesis by increasing ERK1/2 expression, and suppresses astrogenesis by decreasing BMP 2,4 and SMAD 1,5,8 expression in subventricular zone neural stem cells. Life Sci  2011; 89(13-14): 439-49.
[http://dx.doi.org/10.1016/j.lfs.2011.07.003] [PMID: 21843531] 
[186] 
Song L, Shen B, Li Y. Association and contribution of ERK to IL-6-induced activation of signal transducer and activator of transcription in a human myeloma cell line. Chin Med J (Engl)  2001; 114(9): 954-957 [Engl].
[PMID: 11780390] 
[187] 
Song J, Kumar BK, Kang S, Park KA, Lee WT, Lee JE. The effect of agmatine on expression of IL-1β and TLX which promotes neuronal differentiation in lipopolysaccharide-treated neural progenitors. Exp Neurobiol  2013; 22(4): 268-76.
[http://dx.doi.org/10.5607/en.2013.22.4.268] [PMID: 24465142] 
[188] 
Lippi A, Domingues R, Setz C, Outeiro TF, Krisko A. SARS-CoV-2: At the crossroad between aging and neurodegeneration. Mov Disord  2020; 35(5): 716-20.
[http://dx.doi.org/10.1002/mds.28084] [PMID: 32291797] 
[189] 
Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature  2020; 583(7816): 459-68.
[http://dx.doi.org/10.1038/s41586-020-2286-9] [PMID: 32353859] 
[190] 
Shi CS, Qi HY, Boularan C, et al. SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J Immunol  2014; 193(6): 3080-9.
[http://dx.doi.org/10.4049/jimmunol.1303196] [PMID: 25135833] 
[191] 
Ye Z, Wong CK, Li P, Xie Y. A SARS-CoV protein, ORF-6, induces caspase-3 mediated, ER stress and JNK-dependent apoptosis. Biochim Biophys Acta  2008; 1780(12): 1383-7.
[http://dx.doi.org/10.1016/j.bbagen.2008.07.009] [PMID: 18708124] 
[192] 
Chan CP, Siu KL, Chin KT, Yuen KY, Zheng B, Jin DY. Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein. J Virol  2006; 80(18): 9279-87.
[http://dx.doi.org/10.1128/JVI.00659-06] [PMID: 16940539] 
[193] 
Yang W, Ru Y, Ren J, et al. G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response. Cell Death Dis  2019; 10(12): 946.
[http://dx.doi.org/10.1038/s41419-019-2178-9] [PMID: 31827077] 
[194] 
Song E, Zhang C, Israelow B, et al. Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model bioRxiv  2020; 2020.06.25.169946.
[http://dx.doi.org/10.1101/2020.06.25.169946] 
[195] 
Ramani A, Müller L, Ostermann PN, et al. SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects. 2020; bioRxiv  06575.
[http://dx.doi.org/10.1101/2020.05.20.106575] 
[196] 
Zarifkar A, Choopani S, Ghasemi R, et al. Agmatine prevents LPS-induced spatial memory impairment and hippocampal apoptosis. Eur J Pharmacol  2010; 634(1-3): 84-8.
[http://dx.doi.org/10.1016/j.ejphar.2010.02.029] 
[197] 
Moosavi M, Zarifkar AH, Farbood Y, Dianat M, Sarkaki A, Ghasemi R. Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption. Eur J Pharmacol  2014; 736: 107-14.
[http://dx.doi.org/10.1016/j.ejphar.2014.03.041] [PMID: 24769303] 
[198] 
Lee SH, Oh SH, Park KA, Lee WT, Lee JE. The effects of agmatine on apoptosis induced by capsaicin in mouse hippocampal neuron. Korean J Anat  2000; 33(6): 733-42.
[199] 
Hooshmandi E, Ghasemi R, Iloun P, Moosavi M. The neuroprotective effect of agmatine against amyloid β-induced apoptosis in primary cultured hippocampal cells involving ERK, Akt/GSK-3β, and TNF-α. Mol Biol Rep  2019; 46(1): 489-96.
[http://dx.doi.org/10.1007/s11033-018-4501-4] [PMID: 30474774] 
[200] 
Amiri E, Ghasemi R, Moosavi M. Agmatine protects against 6-OHDA-induced apoptosis; and ERK and Akt/GSK disruption in SH-SY5Y Cells. Cell Mol Neurobiol  2016; 36(6): 829-38.
[http://dx.doi.org/10.1007/s10571-015-0266-7] [PMID: 26346882] 
[201] 
Condello S, Currò M, Ferlazzo N, Caccamo D, Satriano J, Ientile R. Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells. J Neurochem  2011; 116(1): 67-75.
[http://dx.doi.org/10.1111/j.1471-4159.2010.07085.x] [PMID: 21044082] 
[202] 
Arndt MA, Battaglia V, Parisi E, et al. The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis. Am J Physiol Cell Physiol  2009; 296(6): C1411-9.
[http://dx.doi.org/10.1152/ajpcell.00529.2008] [PMID: 19321739] 
[203] 
Gardini G, Cabella C, Cravanzola C, et al. Agmatine induces apoptosis in rat hepatocyte cultures. J Hepatol  2001; 35(4): 482-9.
[http://dx.doi.org/10.1016/S0168-8278(01)00153-2] [PMID: 11682032] 
[204] 
Paizis G, Tikellis C, Cooper ME, et al. Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut  2005; 54(12): 1790-6.
[http://dx.doi.org/10.1136/gut.2004.062398] [PMID: 16166274] 
[205] 
Clarke NE, Belyaev ND, Lambert DW, Turner AJ. Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress. Clin Sci (Lond)  2014; 126(7): 507-16.
[http://dx.doi.org/10.1042/CS20130291] [PMID: 24147777] 
[206] 
Pasquier C, Robichon A. SARS-CoV-2 might manipulate against its host the immunity RNAi/Dicer/Ago system 2020.bioRxiv 
[http://dx.doi.org/10.1101/2020.04.08.031856] 
[207] 
Horyn O, Luhovyy B, Lazarow A, et al. Biosynthesis of agmatine in isolated mitochondria and perfused rat liver: studies with 15N-labelled arginine. Biochem J  2005; 388(Pt 2): 419-25.
[http://dx.doi.org/10.1042/BJ20041260] [PMID: 15656789] 
[208] 
Li G, Regunathan S, Reis DJ. Agmatine is synthesized by a mitochondrial arginine decarboxylase in rat brain. Ann N Y Acad Sci  1995; 763: 325-9.
[http://dx.doi.org/10.1111/j.1749-6632.1995.tb32418.x] [PMID: 7677342] 
[209] 
Sastre M, Regunathan S, Galea E, Reis DJ. Agmatinase activity in rat brain: a metabolic pathway for the degradation of agmatine. J Neurochem  1996; 67(4): 1761-5.
[http://dx.doi.org/10.1046/j.1471-4159.1996.67041761.x] [PMID: 8858963] 
[210] 
Tesson F, Limon-Boulez I, Urban P, et al. Localization of I2-imidazoline binding sites on monoamine oxidases. J Biol Chem  1995; 270(17): 9856-61.
[http://dx.doi.org/10.1074/jbc.270.17.9856] [PMID: 7730367] 
[211] 
Salvi M, Battaglia V, Mancon M, et al. Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism. Biochem J  2006; 396(2): 337-45.
[http://dx.doi.org/10.1042/BJ20060003] [PMID: 16509824] 
[212] 
Grillo MA, Battaglia V, Colombatto S, et al. Inhibition of agmatine transport in liver mitochondria by new charge-deficient agmatine analogues. Biochem Soc Trans  2007; 35(Pt 2): 401-4.
[http://dx.doi.org/10.1042/BST0350401] [PMID: 17371286] 
[213] 
Battaglia V, Grancara S, Mancon M, et al. Agmatine transport in brain mitochondria: a different mechanism from that in liver mitochondria. Amino Acids  2010; 38(2): 423-30.
[http://dx.doi.org/10.1007/s00726-009-0401-1] [PMID: 19997762] 
[214] 
Battaglia V, Rossi CA, Colombatto S, Grillo MA, Toninello A. Different behavior of agmatine in liver mitochondria: inducer of oxidative stress or scavenger of reactive oxygen species? Biochim Biophys Acta  2007; 1768(5): 1147-53.
[http://dx.doi.org/10.1016/j.bbamem.2007.01.011] [PMID: 17316555] 
[215] 
Battaglia V, Grancara S, Satriano J, Saccoccio S, Agostinelli E, Toninello A. Agmatine prevents the Ca(2+)-dependent induction of permeability transition in rat brain mitochondria. Amino Acids  2010; 38(2): 431-7.
[http://dx.doi.org/10.1007/s00726-009-0402-0] [PMID: 20012118] 
[216] 
Gentimir C, Acatrinei D, Zaharia C, et al. Biochemical effects of polyamines and Pre-B lymphocytes apoptosis. Rev Chim  2016; 67(2): 353-6.
[217] 
Martinis P, Grancara S, Kanamori Y, et al. Involvement of the biogenic active amine agmatine in mitochondrial membrane permeabilization and release of pro-apoptotic factors. Amino Acids  2020; 52(2): 161-9.
[http://dx.doi.org/10.1007/s00726-019-02791-6] [PMID: 31654209] 
[218] 
Cunningham CN, Baughman JM, Phu L, et al. USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria. Nat Cell Biol  2015; 17(2): 160-9.
[http://dx.doi.org/10.1038/ncb3097] [PMID: 25621951] 
[219] 
Tzimas C, Michailidou G, Arsenakis M, Kieff E, Mosialos G, Hatzivassiliou EG. Human ubiquitin specific protease 31 is a deubiquitinating enzyme implicated in activation of nuclear factor-kappaB. Cell Signal  2006; 18(1): 83-92.
[http://dx.doi.org/10.1016/j.cellsig.2005.03.017] [PMID: 16214042] 
[220] 
Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell  2005; 122(5): 669-82.
[http://dx.doi.org/10.1016/j.cell.2005.08.012] [PMID: 16125763] 
[221] 
Dantzer R. Neuroimmune interactions: From the brain to the immune system and vice versa. Physiol Rev  2018; 98(1): 477-504.
[http://dx.doi.org/10.1152/physrev.00039.2016] [PMID: 29351513] 
[222] 
Bauer ME, Teixeira AL. Inflammation in psychiatric disorders: what comes first? Ann N Y Acad Sci  2019; 1437(1): 57-67.
[http://dx.doi.org/10.1111/nyas.13712] [PMID: 29752710] 
[223] 
Dunn AJ, Wang J, Ando T. Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv Exp Med Biol  1999; 461: 117-27.
[http://dx.doi.org/10.1007/978-0-585-37970-8_8] [PMID: 10442171] 
[224] 
Maes M. Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry  1995; 19(1): 11-38.
[http://dx.doi.org/10.1016/0278-5846(94)00101-M] [PMID: 7708925] 
[225] 
Neis VB, Manosso LM, Moretti M, Freitas AE, Daufenbach J, Rodrigues AL. Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration. Behav Brain Res  2014; 261: 336-44.
[http://dx.doi.org/10.1016/j.bbr.2013.12.038] [PMID: 24406719] 
[226] 
Piletz JE, Chikkala DN, Ernsberger P. Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. J Pharmacol Exp Ther  1995; 272(2): 581-7.
[PMID: 7853171] 
[227] 
Li YF, Gong ZH, Cao JB, Wang HL, Luo ZP, Li J. Antidepressant-like effect of agmatine and its possible mechanism. Eur J Pharmacol  2003; 469(1-3): 81-8.
[http://dx.doi.org/10.1016/S0014-2999(03)01735-7] [PMID: 12782188] 
[228] 
Zomkowski AD, Hammes L, Lin J, Calixto JB, Santos AR, Rodrigues AL. Agmatine produces antidepressant-like effects in two models of depression in mice. Neuroreport  2002; 13(4): 387-91.
[http://dx.doi.org/10.1097/00001756-200203250-00005] [PMID: 11930146] 
[229] 
Neis VB, Moretti M, Manosso LM, Lopes MW, Leal RB, Rodrigues AL. Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice. Pharmacol Biochem Behav  2015; 130: 9-14.
[http://dx.doi.org/10.1016/j.pbb.2014.12.009] [PMID: 25553821] 
[230] 
Dias Elpo Zomkowski A, Oscar Rosa A, Lin J, Santos AR, Calixto JB, Lúcia Severo Rodrigues A. Evidence for serotonin receptor subtypes involvement in agmatine antidepressant like-effect in the mouse forced swimming test. Brain Res  2004; 1023(2): 253-63.
[http://dx.doi.org/10.1016/j.brainres.2004.07.041] [PMID: 15374751] 
[231] 
Jiang XZ, Li YF, Zhang YZ, Chen H-X, Li J, Wang N-P. [5-HT1A/1B receptors, alpha2-adrenoceptors and the post-receptor adenylate cyclase activation in the mice brain are involved in the antidepressant-like action of agmatine]. Yao Xue Xue Bao  2008; 43(5): 467-73.
[PMID: 18717332] 
[232] 
Zomkowski AD, Santos AR, Rodrigues AL. Evidence for the involvement of the opioid system in the agmatine antidepressant- like effect in the forced swimming test. Neurosci Lett  2005; 381(3): 279-83.
[http://dx.doi.org/10.1016/j.neulet.2005.02.026] [PMID: 15896484] 
[233] 
Taksande BG, Faldu DS, Dixit MP, et al. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice. Eur J Pharmacol  2013; 720(1-3): 115-20.
[http://dx.doi.org/10.1016/j.ejphar.2013.10.041] [PMID: 24183973] 
[234] 
Kotagale NR, Paliwal NP, Aglawe MM, Umekar MJ, Taksande BG. Possible involvement of neuropeptide Y Y1 receptors in antidepressant like effect of agmatine in rats. Peptides  2013; 47: 7-11.
[http://dx.doi.org/10.1016/j.peptides.2013.04.018] [PMID: 23816796] 
[235] 
Neis VB, Moretti M, Bettio LE, et al. Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling. Eur Neuropsychopharmacol  2016; 26(6): 959-71.
[http://dx.doi.org/10.1016/j.euroneuro.2016.03.009] [PMID: 27061850] 
[236] 
Neis VB, Rosado AF, Olescowicz G, et al. The involvement of GABAergic system in the antidepressant-like effect of agmatine. Naunyn Schmiedebergs Arch Pharmacol  2020; 393(10): 1931-9.
[http://dx.doi.org/10.1007/s00210-020-01910-5] [PMID: 32447465] 
[237] 
Gawali NB, Bulani VD, Chowdhury AA, Deshpande PS, Nagmoti DM, Juvekar AR. Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators. Pharmacol Biochem Behav  2016; 149: 1-8.
[http://dx.doi.org/10.1016/j.pbb.2016.07.004] [PMID: 27453424] 
[238] 
Freitas AE, Egea J, Buendia I, et al. Agmatine, by improving neuroplasticity markers and inducing Nrf2, prevents corticosterone-induced depressive-like behavior in mice. Mol Neurobiol  2016; 53(5): 3030-45.
[http://dx.doi.org/10.1007/s12035-015-9182-6] [PMID: 25966970] 
[239] 
Neis VB, Bettio LB, Moretti M, et al. Single administration of agmatine reverses the depressive-like behavior induced by corticosterone in mice: Comparison with ketamine and fluoxetine. Pharmacol Biochem Behav  2018; 173: 44-50.
[http://dx.doi.org/10.1016/j.pbb.2018.08.005] [PMID: 30125592] 
[240] 
Kotagale N, Rahmatkar S, Chauragade S, et al. Involvement of hippocampal agmatine in β1-42 amyloid induced memory impairment, neuroinflammation and BDNF signaling disruption in mice. Neurotoxicology  2020; 80: 1-11.
[http://dx.doi.org/10.1016/j.neuro.2020.06.002] [PMID: 32522471] 
[241] 
Kotagale N, Deshmukh R, Dixit M, Fating R, Umekar M, Taksande B. Agmatine ameliorates manifestation of depression-like behavior and hippocampal neuroinflammation in mouse model of Alzheimer’s disease. Brain Res Bull  2020; 160: 56-64.
[http://dx.doi.org/10.1016/j.brainresbull.2020.04.013] [PMID: 32344125] 
[242] 
Kotagale N, Dixit M, Garmelwar H, Bhondekar S, Umekar M, Taksande B. Agmatine reverses memory deficits induced by Aβ1-42 peptide in mice: A key role of imidazoline receptors. Pharmacol Biochem Behav  2020; 196: 172976.
[http://dx.doi.org/10.1016/j.pbb.2020.172976] [PMID: 32598984] 
[243] 
Halaris A, Zhu H, Feng Y, Piletz JE. Plasma agmatine and platelet imidazoline receptors in depression. Ann N Y Acad Sci  1999; 881: 445-51.
[http://dx.doi.org/10.1111/j.1749-6632.1999.tb09392.x] [PMID: 10415948] 
[244] 
Bernstein HG, Stich C, Jäger K, et al. Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders. Neuropharmacology  2012; 62(1): 237-46.
[http://dx.doi.org/10.1016/j.neuropharm.2011.07.012] [PMID: 21803059] 
[245] 
Shopsin B. The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study. Acta Neuropsychiatr  2013; 25(2): 113-8.
[http://dx.doi.org/10.1111/j.1601-5215.2012.00675.x] [PMID: 25287313] 
[246] 
Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GM. Safety and efficacy of dietary agmatinesulfate in lumbar disc-associated radiculopathy. An open-label, dose-escalating study followed by a randomized, double-blind, placebo-controlled trial. Pain Med  2010; 11(3): 356-68.
[http://dx.doi.org/10.1111/j.1526-4637.2010.00808.x] [PMID: 20447305] 
[247] 
Tohidi V, Hassanzadeh B, Sherwood K, et al. Effect of agmatinesulfate on neuropathic pain. Neurology  2014; 82(10 Supplement): 7-94.
[248] 
Gilad GM, Gilad VH. Long-term (5 years), high daily dosage of dietary agmatine-evidence of safety: a case report. J Med Food  2014; 17(11): 1256-9.
[http://dx.doi.org/10.1089/jmf.2014.0026] [PMID: 25247837] 
[249] 
Li N, Ma WT, Pang M, Fan QL, Hua JL. The commensal microbiota and viral infection: A comprehensive review. Front Immunol  2019; 10: 1551.
[http://dx.doi.org/10.3389/fimmu.2019.01551] [PMID: 31333675] 
[250] 
Zuo T, Zhang F, Lui G C Y, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology  2020; S0016-5085(20): 34701-6.
[http://dx.doi.org/10.1053/j.gastro.2020.05.048] 
[251] 
Nobile B, Durand M, Olié E, et al. Clomipramine could be useful in preventing neurological complications of SARS-CoV-2 infection. J Neuroimmune Pharmacol  2020; 15(3): 347-8.
[http://dx.doi.org/10.1007/s11481-020-09939-2] [PMID: 32601885] 
[252] 
Kawabata T, Ohshima H, Ino M. Occurrence of methylguanidine and agmatine in foods. IARC Sci Publ  1978; 19(19): 415-23.
[PMID: 567182] 
[253] 
Fuell C, Elliott KA, Hanfrey CC, Franceschetti M, Michael AJ. Polyamine biosynthetic diversity in plants and algae. Plant Physiol Biochem  2010; 48(7): 513-20.
[http://dx.doi.org/10.1016/j.plaphy.2010.02.008] [PMID: 20227886] 
[254] 
Osborne DL, Seidel ER. Gastrointestinal luminal polyamines: cellular accumulation and enterohepatic circulation. Am J Physiol  1990; 258(4 Pt 1): G576-84.
[http://dx.doi.org/10.1152/ajpgi.1990.258.4.G576] [PMID: 2333971] 
[255] 
Haenisch B, von Kügelgen I, Bönisch H, et al. Regulatory mechanisms underlying agmatine homeostasis in humans. Am J Physiol Gastrointest Liver Physiol  2008; 295(5): G1104-10.
[http://dx.doi.org/10.1152/ajpgi.90374.2008] [PMID: 18832451] 
[256] 
Molderings GJ, Burian M, Homann J, Nilius M, Göthert M. Potential relevance of agmatine as a virulence factor of Helicobacter pylori. Dig Dis Sci  1999; 44(12): 2397-404.
[http://dx.doi.org/10.1023/A:1026662316750] [PMID: 10630488] 
[257] 
Benamouzig R, Mahé S, Luengo C, Rautureau J, Tomé D. Fasting and postprandial polyamine concentrations in the human digestive lumen. Am J Clin Nutr  1997; 65(3): 766-70.
[http://dx.doi.org/10.1093/ajcn/65.3.766] [PMID: 9062527] 
[258] 
Perlot T, Penninger JM. ACE2 - from the renin-angiotensin system to gut microbiota and malnutrition. Microbes Infect  2013; 15(13): 866-73.
[http://dx.doi.org/10.1016/j.micinf.2013.08.003] [PMID: 23962453] 
[259] 
Dastan A, Kocer I, Erdogan F, Ates O, Kiziltunc A. Agmatine as retinal protection from ischemia-reperfusion injury in guinea pigs. Jpn J Ophthalmol  2009; 53(3): 219-24.
[http://dx.doi.org/10.1007/s10384-009-0660-0] [PMID: 19484439] 
[260] 
Greenberg S, George J, Wollman Y, Shapira I, Laniado S, Keren G. The effect of agmatine administration on ischemic-reperfused isolated rat heart. J Cardiovasc Pharmacol Ther  2001; 6(1): 37-45.
[http://dx.doi.org/10.1177/107424840100600105] [PMID: 11452335] 
[261] 
Sugiura T, Tsutsui H, Takaoka M, et al. Protective effect of agmatine on ischemia/reperfusion-induced renal injury in rats. J Cardiovasc Pharmacol  2008; 51(3): 223-30.
[http://dx.doi.org/10.1097/FJC.0b013e318161d758] [PMID: 18356685] 
[262] 
Sharawy MH, Abdelrahman RS, El-Kashef DH. Agmatine attenuates rhabdomyolysis-induced acute kidney injury in rats in a dose dependent manner. Life Sci  2018; 208: 79-86.
[http://dx.doi.org/10.1016/j.lfs.2018.07.019] [PMID: 30009822] 
[263] 
Ommati MM, Farshad O, Mousavi K, et al. Agmatine alleviates hepatic and renal injury in a rat model of obstructive jaundice. Pharma Nutrition  2020; 100212.
[http://dx.doi.org/10.1016/j.phanu.2020.100212] 
[264] 
El-Kashef DH, El-Kenawi AE, Abdel Rahim M, Suddek GM, Salem HA. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats. Can J Physiol Pharmacol  2016; 94(3): 278-86.
[http://dx.doi.org/10.1139/cjpp-2015-0321] [PMID: 26641937] 
[265] 
Salihoglu YS, Elri T, Gulle K, et al. Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C. Ren Fail  2016; 38(9): 1496-502.
[http://dx.doi.org/10.1080/0886022X.2016.1227919] [PMID: 27604130] 
[266] 
Marx M, Trittenwein G, Aufricht C, Hoeger H, Lubec B. Agmatine and spermidine reduce collagen accumulation in kidneys of diabetic db/db mice. Nephron J  1995; 69(2): 155-8.
[http://dx.doi.org/10.1159/000188432] [PMID: 7723898] 
[267] 
Al Masri AA, El Eter E. Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats. World J Gastroenterol  2012; 18(18): 2188-96.
[http://dx.doi.org/10.3748/wjg.v18.i18.2188] [PMID: 22611311] 
[268] 
Sugiura T, Kobuchi S, Tsutsui H, et al. Preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Eur J Pharmacol  2009; 603(1-3): 108-13.
[http://dx.doi.org/10.1016/j.ejphar.2008.11.062] [PMID: 19105953] 
[269] 
Paz Ocaranza M, Riquelme JA, García L, et al. Counter-regulatory renin-angiotensin system in cardiovascular disease. Nat Rev Cardiol  2020; 17(2): 116-29.
[http://dx.doi.org/10.1038/s41569-019-0244-8] [PMID: 31427727] 
[270] 
Lambert DW, Yarski M, Warner FJ, et al. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). J Biol Chem  2005; 280(34): 30113-9.
[http://dx.doi.org/10.1074/jbc.M505111200] [PMID: 15983030] 
[271] 
Haga S, Yamamoto N, Nakai-Murakami C, et al. Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry. Proc Natl Acad Sci USA  2008; 105(22): 7809-14.
[http://dx.doi.org/10.1073/pnas.0711241105] [PMID: 18490652] 
[272] 
Jia HP, Look DC, Tan P, et al. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am J Physiol Lung Cell Mol Physiol  2009; 297(1): L84-96.
[http://dx.doi.org/10.1152/ajplung.00071.2009] [PMID: 19411314] 
[273] 
Cao Y, Li L, Feng Z, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov  2020; 6: 11.
[http://dx.doi.org/10.1038/s41421-020-0147-1] [PMID: 32133153] 
[274] 
Chiappelli F. Towards Neuro-CoViD-19. Bioinformation  2020; 16(4): 288-92.
[http://dx.doi.org/10.6026/97320630016288] [PMID: 32773986] 
[275] 
Zamai L. The Yin and Yang of ACE/ACE2 pathways: The rationale for the use of renin-angiotensin system inhibitors in COVID-19 Patients. Cells  2020; 9(7): 1704.
[http://dx.doi.org/10.3390/cells9071704] [PMID: 32708755] 
[276] 
Jiang T, Xue LJ, Yang Y, et al. AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation. Aging (Albany NY)  2018; 10(4): 645-57.
[http://dx.doi.org/10.18632/aging.101419] [PMID: 29667931] 
[277] 
Tao MX, Xue X, Gao L, et al. Involvement of angiotensin-(1-7) in the neuroprotection of captopril against focal cerebral ischemia. Neurosci Lett  2018; 687: 16-21.
[http://dx.doi.org/10.1016/j.neulet.2018.09.024] [PMID: 30219484] 
[278] 
Stone RE, Liu S, Levy AM, et al. Activation of the protective arm of the renin angiotensin system in demyelinating disease. J Neuroimmune Pharmacol  2020; 15(2): 249-63.
[http://dx.doi.org/10.1007/s11481-019-09894-7] [PMID: 31828731] 
[279] 
Evans CE, Miners JS, Piva G, et al. ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of Alzheimer’s disease. Acta Neuropathol  2020; 139(3): 485-502.
[http://dx.doi.org/10.1007/s00401-019-02098-6] [PMID: 31982938] 
[280] 
Rocha NP, Simoes E Silva AC, Prestes TRR, et al. RAS in the central nervous system: Potential role in neuropsychiatric disorders. Curr Med Chem  2018; 25(28): 3333-52.
[http://dx.doi.org/10.2174/0929867325666180226102358] [PMID: 29484978] 
[281] 
Alenina N, Bader M. ACE2 in brain physiology and pathophysiology: Evidence from transgenic animal models. Neurochem Res  2019; 44(6): 1323-9.
[http://dx.doi.org/10.1007/s11064-018-2679-4] [PMID: 30443713] 
[282] 
Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/angiotensin 1-7 axis of the renin-angiotensin system in heart failure. Circ Res  2016; 118(8): 1313-26.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.307708] [PMID: 27081112] 
[283] 
Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med  2005; 11(8): 875-9.
[http://dx.doi.org/10.1038/nm1267] [PMID: 16007097] 
[284] 
Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature  2005; 436(7047): 112-6.
[http://dx.doi.org/10.1038/nature03712] [PMID: 16001071] 
[285] 
Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell  2020; 181(4): 905-913.e7.
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836] 
[286] 
Khan A, Benthin C, Zeno B, et al. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care  2017; 21(1): 234.
[http://dx.doi.org/10.1186/s13054-017-1823-x] [PMID: 28877748] 
[287] 
Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med  2020; 46(4): 586-90.
[http://dx.doi.org/10.1007/s00134-020-05985-9] [PMID: 32125455] 
[288] 
Epelman S, Shrestha K, Troughton RW, et al. Soluble angiotensin-converting enzyme 2 in human heart failure: relation with myocardial function and clinical outcomes. J Card Fail  2009; 15(7): 565-71.
[http://dx.doi.org/10.1016/j.cardfail.2009.01.014] [PMID: 19700132] 
[289] 
Garg M, Burrell LM, Velkoska E, et al. Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study. J Renin Angiotensin Aldosterone Syst  2015; 16(3): 559-69.
[http://dx.doi.org/10.1177/1470320314521086] [PMID: 24505094] 
[290] 
He X, Zhang L, Ran Q, et al. Integrative bioinformatics analysis provides insight into the molecular mechanisms of 2019-nCoV 2020; medRxiv  2020.02.03.20020206.
[http://dx.doi.org/10.1101/2020.02.03.20020206] 
[291] 
Lew RA, Warner FJ, Hanchapola I, et al. Angiotensin-converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor. Exp Physiol  2008; 93(5): 685-93.
[http://dx.doi.org/10.1113/expphysiol.2007.040352] [PMID: 18223027] 
[292] 
Huentelman MJ, Zubcevic J, Hernández Prada JA, et al. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension  2004; 44(6): 903-6.
[http://dx.doi.org/10.1161/01.HYP.0000146120.29648.36] [PMID: 15492138] 
[293] 
Bongetta D, Calloni T, Colombo EV, Versace A, Assietti R. Do matrix metalloproteases mediate the SARS-CoV-2-related damage to the central nervous system? Brain Behav Immun  2020; 88: 35.
[http://dx.doi.org/10.1016/j.bbi.2020.05.050] [PMID: 32446945] 
[294] 
Muri L, Leppert D, Grandgirard D, Leib SL. MMPs and ADAMs in neurological infectious diseases and multiple sclerosis. Cell Mol Life Sci  2019; 76(16): 3097-116.
[http://dx.doi.org/10.1007/s00018-019-03174-6] [PMID: 31172218] 
[295] 
Kim JH, Lee YW, Kim JY, Lee WT, Park KA, Lee JE. The effect of agmatine on expression of MMP2 andMMP9 in cerebral ischemia. Anat Cell Biol  2008; 41(1): 97-104.
[296] 
Jung HJ, Yang MZ, Kwon KH, et al. Endogenous agmatine inhibits cerebral vascular matrix metalloproteinases expression by regulating activating transcription factor 3 and endothelial nitric oxide synthesis. Curr Neurovasc Res  2010; 7(3): 201-12.
[http://dx.doi.org/10.2174/156720210792231804] [PMID: 20560878] 
[297] 
Yang MZ, Mun CH, Choi YJ, et al. Agmatine inhibits matrix metalloproteinase-9 via endothelial nitric oxide synthase in cerebral endothelial cells. Neurol Res  2007; 29(7): 749-54.
[http://dx.doi.org/10.1179/016164107X208103] [PMID: 17588309] 
[298] 
Becker GL, Sielaff F, Than ME, et al. Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics. J Med Chem  2010; 53(3): 1067-75.
[http://dx.doi.org/10.1021/jm9012455] [PMID: 20038105] 
[299] 
Lim HA, Joy J, Hill J, San Brian Chia C. Novel agmatine and agmatine-like peptidomimetic inhibitors of the West Nile virus NS2B/NS3 serine protease. Eur J Med Chem  2011; 46(7): 3130-4.
[http://dx.doi.org/10.1016/j.ejmech.2011.04.055] [PMID: 21565434] 
[300] 
Lim HA, Ang MJ, Joy J, et al. Novel agmatine dipeptide inhibitors against the West Nile virus NS2B/NS3 protease: a P3 and N- cap optimization study. Eur J Med Chem  2013; 62: 199-205.
[http://dx.doi.org/10.1016/j.ejmech.2012.12.043] [PMID: 23353753] 
[301] 
Ang MJY, Li Z, Lim HA, et al. A P2 and P3 substrate specificity comparison between the Murray Valley encephalitis and West Nile virus NS2B/NS3 protease using C-terminal agmatine dipeptides. Peptides  2014; 52: 49-52.
[http://dx.doi.org/10.1016/j.peptides.2013.12.002] [PMID: 24333681] 
[302] 
Donalisio M, Quaranta P, Chiuppesi F, et al. The AGMA1 poly(amidoamine) inhibits the infectivity of herpes simplex virus in cell lines, in human cervicovaginal histocultures, and in vaginally infected mice. Biomaterials  2016; 85: 40-53.
[http://dx.doi.org/10.1016/j.biomaterials.2016.01.055] [PMID: 26854390] 
[303] 
Cagno V, Donalisio M, Bugatti A, et al. The agmatine-containing poly(amidoamine) polymer AGMA1 binds cell surface heparan sulfates and prevents attachment of mucosal human papillomaviruses. Antimicrob Agents Chemother  2015; 59(9): 5250-9.
[http://dx.doi.org/10.1128/AAC.00443-15] [PMID: 26077258] 
[304] 
Costa VV, Del Sarto JL, Rocha RF, et al. N-Methyl-d-Aspartate (NMDA) receptor blockade prevents neuronal death induced by zika virus infection. MBio  2017; 8(2): e00350-17.
[http://dx.doi.org/10.1128/mBio.00350-17] [PMID: 28442607] 
[305] 
Vlassara H, Striker LJ, Teichberg S, Fuh H, Li YM, Steffes M. Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats. Proc Natl Acad Sci USA  1994; 91(24): 11704-8.
[http://dx.doi.org/10.1073/pnas.91.24.11704] [PMID: 7972128] 
[306] 
Mounce BC, Olsen ME, Vignuzzi M, Connor JH. Polyamines and their role in virus infection. Microbiol Mol Biol Rev  2017; 81(4): e00029-17.
[http://dx.doi.org/10.1128/MMBR.00029-17] [PMID: 28904024] 
[307] 
Satriano J, Matsufuji S, Murakami Y, et al. Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. J Biol Chem  1998; 273(25): 15313-6.
[http://dx.doi.org/10.1074/jbc.273.25.15313] [PMID: 9624108] 
[308] 
Vargiu C, Cabella C, Belliardo S, Cravanzola C, Grillo MA, Colombatto S. Agmatine modulates polyamine content in hepatocytes by inducing spermidine/spermine acetyltransferase. Eur J Biochem  1999; 259(3): 933-8.
[http://dx.doi.org/10.1046/j.1432-1327.1999.00126.x] [PMID: 10092884] 
[309] 
Wang JF, Su RB, Wu N, et al. Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism. Acta Pharmacol Sin  2005; 26(5): 616-22.
[PMID: 15842783] 
[310] 
Mistry SK, Burwell TJ, Chambers RM, et al. Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus. Am J Physiol Gastrointest Liver Physiol  2002; 282(2): G375-81.
[http://dx.doi.org/10.1152/ajpgi.00386.2001] [PMID: 11804860] 
[311] 
Hoffman LA, Vilensky JA. Encephalitis lethargica: 100 years after the epidemic. Brain  2017; 140(8): 2246-51.
[http://dx.doi.org/10.1093/brain/awx177] [PMID: 28899018] 
[312] 
Kępińska AP, Iyegbe CO, Vernon AC, Yolken R, Murray RM, Pollak TA. Schizophrenia and influenza at the centenary of the 1918-1919 Spanish influenza pandemic: Mechanisms of psychosis risk. Front Psychiatry  2020; 11: 72.
[http://dx.doi.org/10.3389/fpsyt.2020.00072] [PMID: 32174851] 
[313] 
Kim JE, Heo JH, Kim HO, et al. Neurological complications during treatment of Middle East respiratory syndrome. J Clin Neurol  2017; 13(3): 227-33.
[http://dx.doi.org/10.3988/jcn.2017.13.3.227] [PMID: 28748673] 
[314] 
Tsai LK, Hsieh ST, Chao CC, et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol  2004; 61(11): 1669-73.
[http://dx.doi.org/10.1001/archneur.61.11.1669] [PMID: 15534177] 
[315] 
Paterson R W, Benjamin L A, Mehta P R, et al. Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes. Brain Communications  2021; 3(3): fcab099.
[http://dx.doi.org/10.1093/braincomms/fcab099] 
[316] 
Quincozes-Santos A, Rosa RL, Tureta EF, et al. COVID-19 impacts the expression of molecular markers associated with neuropsychiatric disorders. Brain Behav Immun  2021; 11: 100196.
[http://dx.doi.org/10.1016/j.bbih.2020.100196] [PMID: 33521688] 
[317] 
Edén A, Simrén J, Price RW, Zetterberg H, Gisslén M. Neurochemical biomarkers to study CNS effects of COVID-19: A narrative review and synthesis. J Neurochem  2021; 159(1): 61-77.
[http://dx.doi.org/10.1111/jnc.15459] [PMID: 34170549] 
[318] 
Ciaccio M, Lo Sasso B, Scazzone C, et al. COVID-19 and Alzheimer’s disease. Brain Sci  2021; 11(3): 305.
[http://dx.doi.org/10.3390/brainsci11030305] [PMID: 33673697] 
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DOI https://dx.doi.org/10.2174/2666796703666220106112842	Print ISSN 2666-7967
Publisher Name Bentham Science Publisher	Online ISSN 2666-7975
Coronaviruses

Is There a Rendezvous for SARS-CoV-2 and Agmatine?

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