Abstract
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that regulates energy metabolism mainly through the pentose phosphate pathway (PPP). It is well known that this enzyme participates in the antioxidant/oxidant balance via the synthesis of energy-rich molecules: nicotinamide adenine dinucleotide phosphate reduced (NADPH), the reduced form of flavin adenine dinucleotide (FADH) and glutathione (GSH), controlling reactive oxygen species generation. Coronavirus disease 19 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health problem that has caused approximately 4.5 million deaths since December 2019. Concerning the role of G6PD in COVID-19 development, it is known from the existing literature that G6PD-deficient patients infected with SARS-CoV-2 are more susceptible to thrombosis and hemolysis, suggesting that G6PD deficiency facilitates infection by SARS-CoV-2. Concerning G6PD and neuropathology, it has been observed that deficiency of this enzyme is also present with an increase in oxidative markers. Concerning the role of G6PD and the neurological manifestations of COVID-19, it has been reported that the enzymatic deficiency in patients infected with SARSCoV- 2 exacerbates the disease, and, in some clinical reports, an increase in hemolysis and thrombosis was observed when patients were treated with hydroxychloroquine (OH-CQ), a drug with oxidative properties. In the present work, we summarize the evidence of the role of G6PD in COVID- 19 and its possible role in the generation of oxidative stress and glucose metabolism deficits, and inflammation present in this respiratory disease and its progression including neurological manifestations.
Keywords: G6PD, GSH, COVID-19, SARS-CoV-2, Hydroxychloroquine, Reactive oxygen species.
[http://dx.doi.org/10.1038/s41579-021-00535-6] [PMID: 33753932]
[http://dx.doi.org/10.1136/bmj.2.5297.82] [PMID: 14455113]
[http://dx.doi.org/10.7759/cureus.7423] [PMID: 32337143]
[http://dx.doi.org/10.1101/2020.09.24.312553]
[http://dx.doi.org/10.1038/s41392-020-0190-2] [PMID: 32533062]
[http://dx.doi.org/10.1016/S0140-6736(03)14630-2] [PMID: 14585636]
[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508]
[http://dx.doi.org/10.1016/j.chom.2020.02.001] [PMID: 32035028]
[http://dx.doi.org/10.1101/2020.10.21.349225]
[http://dx.doi.org/10.1016/j.antiviral.2020.104742] [PMID: 32057769]
[http://dx.doi.org/10.3390/v4061011] [PMID: 22816037]
[http://dx.doi.org/10.1128/JVI.77.16.8801-8811.2003] [PMID: 12885899]
[http://dx.doi.org/10.1038/s41423-020-0400-4] [PMID: 32203189]
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[http://dx.doi.org/10.1016/j.micpath.2020.104641] [PMID: 33242646]
[http://dx.doi.org/10.1038/s41579-020-00468-6] [PMID: 33116300]
[http://dx.doi.org/10.1001/jamapediatrics.2020.4573] [PMID: 32975552]
[http://dx.doi.org/10.1126/science.abe8372] [PMID: 33531384]
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[http://dx.doi.org/10.1093/infdis/jiaa691] [PMID: 33119738]
[http://dx.doi.org/10.1159/000508233] [PMID: 32396903]
[http://dx.doi.org/10.1007/s10753-020-01337-3] [PMID: 33029758]
[http://dx.doi.org/10.1136/bmj.m1198] [PMID: 32217618]
[http://dx.doi.org/10.1128/JVI.00127-09] [PMID: 19420084]
[http://dx.doi.org/10.1016/j.jinf.2020.03.005] [PMID: 32171866]
[http://dx.doi.org/10.1371/journal.pone.0018918] [PMID: 21526215]
[http://dx.doi.org/10.1165/ajrcmb.13.2.7626291] [PMID: 7626291]
[http://dx.doi.org/10.1016/j.arcmed.2020.04.019] [PMID: 32402576]
[http://dx.doi.org/10.1089/ars.2014.5907] [PMID: 24673169]
[PMID: 24217073]
[http://dx.doi.org/10.3109/10715769209049163] [PMID: 1321077]
[http://dx.doi.org/10.1038/s41577-020-0311-8] [PMID: 32346093]
[http://dx.doi.org/10.1371/journal.pone.0235458] [PMID: 32645044]
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317015] [PMID: 32264791]
[http://dx.doi.org/10.5494/wjh.v2.i4.34] [PMID: 24587981]
[http://dx.doi.org/10.1038/cr.2008.15] [PMID: 18227861]
[http://dx.doi.org/10.1038/s41467-020-18764-3] [PMID: 33009401]
[http://dx.doi.org/10.2174/1568009617666171002144228] [PMID: 28969555]
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.06.018] [PMID: 34186206]
[http://dx.doi.org/10.1177/2050312121991246] [PMID: 33614035]
[http://dx.doi.org/10.1016/j.arcmed.2021.06.004] [PMID: 34154831]
[http://dx.doi.org/10.1016/j.redox.2021.102181] [PMID: 34768063]
[http://dx.doi.org/10.2478/rjim-2021-0014] [PMID: 33910269]
[http://dx.doi.org/10.12688/f1000research.55166.2] [PMID: 34868558]
[http://dx.doi.org/10.18632/aging.202557] [PMID: 33638944]
[http://dx.doi.org/10.21037/apm-20-1387] [PMID: 33222462]
[http://dx.doi.org/10.1515/znc-2021-0101] [PMID: 34355546]
[http://dx.doi.org/10.3748/wjg.v27.i22.2944] [PMID: 34168400]
[http://dx.doi.org/10.3389/fimmu.2020.598444] [PMID: 33362782]
[http://dx.doi.org/10.3346/jkms.2020.35.e343] [PMID: 32989935]
[http://dx.doi.org/10.1016/j.ccell.2018.03.022] [PMID: 29731393]
[http://dx.doi.org/10.1128/MCB.00099-20] [PMID: 32284348]
[http://dx.doi.org/10.1016/j.redox.2013.06.001] [PMID: 24024172]
[PMID: 30317274]
[http://dx.doi.org/10.1086/528377] [PMID: 18269318]
[http://dx.doi.org/10.3389/fmed.2020.584112] [PMID: 33195336]
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.10.002] [PMID: 33038530]
[http://dx.doi.org/10.1016/j.mayocp.2020.05.035] [PMID: 32680625]
[http://dx.doi.org/10.1096/fj.00-0893fje] [PMID: 11481225]
[http://dx.doi.org/10.1016/j.abb.2018.12.023] [PMID: 30582899]
[http://dx.doi.org/10.3390/ijms151121179] [PMID: 25407525]
[http://dx.doi.org/10.1016/j.clim.2020.108544] [PMID: 32707089]
[http://dx.doi.org/10.1007/978-3-319-63245-2_8] [PMID: 29047084]
[http://dx.doi.org/10.1186/s12866-020-01890-9] [PMID: 32689931]
[http://dx.doi.org/10.1111/j.1753-4887.1992.tb02456.x] [PMID: 1579264]
[http://dx.doi.org/10.2174/1570162X13666150313152422] [PMID: 25771095]
[http://dx.doi.org/10.1089/ars.2011.4307] [PMID: 22799599]
[http://dx.doi.org/10.3390/medicina56080386] [PMID: 32752010]
[http://dx.doi.org/10.3390/molecules16032032] [PMID: 21358592]
[http://dx.doi.org/10.1016/0140-6736(92)90939-Z] [PMID: 1348307]
[http://dx.doi.org/10.1111/trf.14318] [PMID: 28921542]
[http://dx.doi.org/10.1111/trf.14442] [PMID: 29322519]
[http://dx.doi.org/10.1073/pnas.94.5.1967] [PMID: 9050888]
[http://dx.doi.org/10.1016/S0014-5793(98)01174-0] [PMID: 9801159]
[http://dx.doi.org/10.1111/bph.15085] [PMID: 32346862]
[http://dx.doi.org/10.1007/s00726-018-2559-x] [PMID: 29626298]
[http://dx.doi.org/10.1155/2012/736837] [PMID: 22500213]
[http://dx.doi.org/10.1080/713803463] [PMID: 10791914]
[http://dx.doi.org/10.1016/0891-5849(94)00198-S] [PMID: 7750801]
[http://dx.doi.org/10.1089/ars.2014.6142] [PMID: 25556665]
[http://dx.doi.org/10.1016/j.bcmd.2008.12.005] [PMID: 19233695]
[http://dx.doi.org/10.1056/NEJMra1708111] [PMID: 29298156]
[http://dx.doi.org/10.1016/j.arcmed.2020.06.006] [PMID: 32600868]
[http://dx.doi.org/10.7205/MILMED.171.9.905] [PMID: 17036616]
[http://dx.doi.org/10.1186/1471-2431-13-137] [PMID: 24016342]
[http://dx.doi.org/10.1016/j.hemonc.2020.04.002] [PMID: 32325028]
[http://dx.doi.org/10.1073/pnas.77.5.2810] [PMID: 6930669]
[http://dx.doi.org/10.1104/pp.107.108423] [PMID: 17993547]
[http://dx.doi.org/10.1016/j.plaphy.2016.04.013] [PMID: 27085599]
[PMID: 3887862]
[http://dx.doi.org/10.3390/ijms17122069] [PMID: 27941691]
[http://dx.doi.org/10.1016/S0969-2126(00)00104-0] [PMID: 10745013]
[http://dx.doi.org/10.1107/S0907444905002350] [PMID: 15858258]
[http://dx.doi.org/10.1056/NEJM199101173240306] [PMID: 1984194]
[http://dx.doi.org/10.1182/blood.2019000944] [PMID: 32702756]
[http://dx.doi.org/10.1002/iub.137] [PMID: 18942156]
[http://dx.doi.org/10.1007/s00277-021-04395-1] [PMID: 33439304]
[http://dx.doi.org/10.1080/20477724.2020.1751388] [PMID: 32286926]
[http://dx.doi.org/10.1136/bcr-2013-201432]]
[http://dx.doi.org/10.1056/NEJMc2009787] [PMID: 32343504]
[http://dx.doi.org/10.1038/s41525-020-00143-y] [PMID: 32864162]
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[http://dx.doi.org/10.1097/BOR.0000000000000500] [PMID: 29517495]
[http://dx.doi.org/10.1099/0022-1317-62-1-91] [PMID: 6290597]
[http://dx.doi.org/10.1073/pnas.0306446101] [PMID: 15010527]
[http://dx.doi.org/10.1128/JVI.78.11.5642-5650.2004] [PMID: 15140961]
[http://dx.doi.org/10.1097/00126334-200403010-00002] [PMID: 15076236]
[http://dx.doi.org/10.1089/aid.1990.6.481] [PMID: 1692728]
[http://dx.doi.org/10.1038/321618a0] [PMID: 3086747]
[http://dx.doi.org/10.1111/j.0001-5172.2004.0302.x] [PMID: 14982575]
[http://dx.doi.org/10.1016/j.ajem.2019.158387] [PMID: 31477360]
[http://dx.doi.org/10.1177/0961203396005001041] [PMID: 8803904]
[http://dx.doi.org/10.1093/jac/dkg319] [PMID: 12837731]
[http://dx.doi.org/10.1080/15563650.2020.1817479] [PMID: 32960100]
[http://dx.doi.org/10.1016/j.crvi.2004.07.010] [PMID: 15506519]
[PMID: 15631380]
[http://dx.doi.org/10.1136/bmj.m1849] [PMID: 32409561]
[http://dx.doi.org/10.1080/23744235.2020.1774644] [PMID: 32496938]
[http://dx.doi.org/10.1111/ejh.13460] [PMID: 32500556]
[http://dx.doi.org/10.2165/11536520-000000000-00000] [PMID: 20701405]
[http://dx.doi.org/10.1111/ejh.13432] [PMID: 32324284]
[http://dx.doi.org/10.1016/j.ejim.2020.04.020] [PMID: 32381323]
[http://dx.doi.org/10.1002/ajh.25862] [PMID: 32390140]
[http://dx.doi.org/10.12659/AJCR.925788] [PMID: 32697769]
[http://dx.doi.org/10.7759/cureus.15232] [PMID: 34178542]
[http://dx.doi.org/10.7812/TPP/20.158] [PMID: 33183501]
[http://dx.doi.org/10.12890/2020_001875] [PMID: 32908842]
[http://dx.doi.org/10.1093/qjmed/hcaa267] [PMID: 32936918]
[http://dx.doi.org/10.1371/journal.pone.0240266] [PMID: 33007039]
[http://dx.doi.org/10.1016/j.bcmd.2020.102484] [PMID: 32836191]
[http://dx.doi.org/10.1016/S1473-3099(18)30348-7] [PMID: 30033231]
[http://dx.doi.org/10.1016/j.neuint.2013.02.005] [PMID: 23416042]
[http://dx.doi.org/10.2174/0929867321666131217153310] [PMID: 24350853]
[http://dx.doi.org/10.1016/j.clp.2016.01.010] [PMID: 27235212]
[http://dx.doi.org/10.1016/j.clp.2016.01.008] [PMID: 27235211]
[http://dx.doi.org/10.1080/10715762.2020.1866757] [PMID: 33401987]
[http://dx.doi.org/10.1002/iub.1017] [PMID: 22431005]
[http://dx.doi.org/10.1007/978-1-4939-2257-4_23] [PMID: 25631020]
[http://dx.doi.org/10.1021/acsnano.6b04108] [PMID: 27666121]
[http://dx.doi.org/10.1016/j.cell.2012.02.032] [PMID: 22424225]
[http://dx.doi.org/10.1111/cns.13711] [PMID: 34369077]
[http://dx.doi.org/10.1212/WNL.0000000000010245] [PMID: 32651291]
[http://dx.doi.org/10.1007/s12031-020-01614-8] [PMID: 32535712]
[http://dx.doi.org/10.1016/0306-9877(80)90026-2] [PMID: 7382887]
[http://dx.doi.org/10.1016/j.neuint.2008.01.009] [PMID: 18308427]
[http://dx.doi.org/10.1016/0022-510X(85)90183-2] [PMID: 4045497]
[http://dx.doi.org/10.1016/j.expneurol.2011.05.024] [PMID: 21684277]
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.11.001] [PMID: 24300239]
[http://dx.doi.org/10.1006/abbi.1999.1404] [PMID: 10510282]
[http://dx.doi.org/10.1159/000110338] [PMID: 8309511]
[http://dx.doi.org/10.1001/archpsyc.1976.01770100064006] [PMID: 971029]
[PMID: 27762116]
[http://dx.doi.org/10.3389/fphys.2020.00694] [PMID: 32714204]
[http://dx.doi.org/10.1007/s11060-018-2911-8] [PMID: 29845423]
[http://dx.doi.org/10.1021/cn400079y] [PMID: 23672460]
[http://dx.doi.org/10.1007/s12035-015-9337-5] [PMID: 26198567]
[http://dx.doi.org/10.1186/s12974-019-1659-1] [PMID: 31805953]
[http://dx.doi.org/10.1002/jcb.29004] [PMID: 31127649]
[http://dx.doi.org/10.1179/135100007X200209] [PMID: 17623517]
[http://dx.doi.org/10.1016/j.gendis.2017.09.001] [PMID: 30258923]
[http://dx.doi.org/10.1080/15257770.2021.1897457] [PMID: 33719907]
[http://dx.doi.org/10.1259/bjrcr.20200098] [PMID: 32922857]
[http://dx.doi.org/10.30621/jbachs.2020.1151]
[http://dx.doi.org/10.1016/j.clinbiochem.2020.09.004] [PMID: 32950470]
[PMID: 23416142]
[PMID: 18946458]
[http://dx.doi.org/10.7573/dic.2020-5-7] [PMID: 32636919]
[http://dx.doi.org/10.4103/jrms.JRMS_322_20] [PMID: 33273937]