Review Article

SARS-Coronavirus 2, A Metabolic Reprogrammer: A Review in the Context of the Possible Therapeutic Strategies

Author(s): P. Gopi, T.R. Anju, V.S. Pillai and M. Veettil*

Volume 23, Issue 8, 2022

Published on: 17 September, 2021

Page: [770 - 781] Pages: 12

DOI: 10.2174/1389450122666210917113842

Price: $65

Abstract

Novel coronavirus, SARS-CoV-2, is advancing at a staggering pace to devastate the health care system and foster concerns over public health. In contrast to the past outbreaks, coronaviruses are not clinging themselves as a strict respiratory virus. Rather, becoming a multifaceted virus, it affects multiple organs by interrupting a number of metabolic pathways leading to significant rates of morbidity and mortality. Following infection, they rigorously reprogram multiple metabolic pathways of glucose, lipid, protein, nucleic acid, and their metabolites to extract adequate energy and carbon skeletons required for their existence and further molecular constructions inside a host cell. Although the mechanism of these alterations is yet to be known, the impact of these reprogramming is reflected in the hyperinflammatory responses, so called cytokine storm and the hindrance of the host immune defence system. The metabolic reprogramming during SARSCoV- 2 infection needs to be considered while devising therapeutic strategies to combat the disease and its further complication. The inhibitors of cholesterol and phospholipids synthesis and cell membrane lipid raft of the host cell can, to a great extent, control the viral load and further infection. Depletion of energy sources by inhibiting the activation of glycolytic and hexosamine biosynthetic pathways can also augment antiviral therapy. The cross talk between these pathways also necessitates the inhibition of amino acid catabolism and tryptophan metabolism. A combinatorial strategy that can address the cross talks between the metabolic pathways might be more effective than a single approach, and the infection stage and timing of therapy will also influence the effectiveness of the antiviral approach. We herein focus on the different metabolic alterations during the course of virus infection that help exploit the cellular machinery and devise a therapeutic strategy that promotes resistance to viral infection and can augment body’s antivirulence mechanisms. This review may cast light on the possibilities of targeting altered metabolic pathways to defend against virus infection in a new perspective.

Keywords: SARS-CoV-2, COVID-19, metabolic reprogramming, therapeutic target, cytokine storm, post COVID disorders.

Graphical Abstract

[1]
Kaur N, Singh R, Dar Z, Bijarnia RK, Dhingra N, Kaur T. Genetic comparison among various coronavirus strains for the identification of potential vaccine targets of SARS-CoV2. Infect Genet Evol 2021; 89: 104490.
[http://dx.doi.org/10.1016/j.meegid.2020.104490] [PMID: 32745811]
[2]
Wille M, Holmes EC. Wild birds as reservoirs for diverse and abundant gamma- and deltacoronaviruses. FEMS Microbiol Rev 2020; 44(5): 631-44.
[http://dx.doi.org/10.1093/femsre/fuaa026] [PMID: 32672814]
[3]
Boley PA, Alhamo MA, Lossie G, et al. Porcine deltacoronavirus infection and transmission in poultry, united states. Emerg Infect Dis 2020; 26(2): 255-65.
[http://dx.doi.org/10.3201/eid2602.190346] [PMID: 31961296]
[4]
Tang S, Mao Y, Jones RM, et al. Aerosol transmission of SARS-CoV-2? Evidence, prevention and control. Environ Int 2020; 144: 106039.
[http://dx.doi.org/10.1016/j.envint.2020.106039] [PMID: 32822927]
[5]
Mayer KA, StAckl J, Zlabinger GJ, Gualdoni GA. Hijacking the supplies: Metabolism as a novel facet of virus-host interaction. Front Immunol 2019; 10: 1533.
[http://dx.doi.org/10.3389/fimmu.2019.01533] [PMID: 31333664]
[6]
Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant 2020; 39(5): 405-7.
[http://dx.doi.org/10.1016/j.healun.2020.03.012] [PMID: 32362390]
[7]
Bornstein SR, Dalan R, Hopkins D, Mingrone G, Boehm BO. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol 2020; 16(6): 297-8.
[http://dx.doi.org/10.1038/s41574-020-0353-9] [PMID: 32242089]
[8]
Deng S-Q, Peng H-J. Characteristics of and public health responses to the coronavirus disease 2019 outbreak in china. J Clin Med 2020; 9(2): 575.
[http://dx.doi.org/10.3390/jcm9020575] [PMID: 32093211]
[9]
Popkin BM, Du S, Green WD, et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obes Rev 2020; 21(11): e13128.
[http://dx.doi.org/10.1111/obr.13128] [PMID: 32845580]
[10]
Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J Endocrinol Metab 2012; 16(Suppl 1): 27-36.
[11]
Karlsson EAMJ, Green WD, Rebeles J, Schultz-Cherry S, Beck M. Influence of obesity on the response to influenza infection and vaccination. In: Johnston R, Ed. Mechanisms and Manifestations of Obesity in Lung Disease. (1st edition.). Cambridge, Massachusetts: Academic Press 2019; pp. 227-59.
[http://dx.doi.org/10.1016/B978-0-12-813553-2.00010-5]
[12]
Bindom SM, Lazartigues E. The sweeter side of ACE2: physiological evidence for a role in diabetes. Mol Cell Endocrinol 2009; 302(2): 193-202.
[http://dx.doi.org/10.1016/j.mce.2008.09.020] [PMID: 18948167]
[13]
He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med 2020; 26(5): 672-5.
[http://dx.doi.org/10.1038/s41591-020-0869-5] [PMID: 32296168]
[14]
To KK, Tsang OT, Leung WS, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis 2020; 20(5): 565-74.
[http://dx.doi.org/10.1016/S1473-3099(20)30196-1] [PMID: 32213337]
[15]
Louie JK, Yang S, Acosta M, et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis 2012; 55(9): 1198-204.
[http://dx.doi.org/10.1093/cid/cis636] [PMID: 22843781]
[16]
Ayres JS. Surviving COVID-19: A disease tolerance perspective. Sci Adv 2020; 6(18): eabc1518.
[17]
Krishna G, Pillai VS, Veettil MV. Approaches and advances in the development of potential therapeutic targets and antiviral agents for the management of SARS-CoV-2 infection. Eur J Pharmacol 2020; 885: 173450.
[http://dx.doi.org/10.1016/j.ejphar.2020.173450] [PMID: 32739174]
[18]
Ajaz S, McPhail MJ, Singh KK, et al. Mitochondrial metabolic manipulation by SARS-CoV-2 in peripheral blood mononuclear cells of patients with COVID-19. Am J Physiol Cell Physiol 2021; 320(1): C57-65.
[http://dx.doi.org/10.1152/ajpcell.00426.2020] [PMID: 33151090]
[19]
Codo AC, Davanzo GG, Monteiro LB, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1Iα/glycolysis-dependent axis. Cell Metab 2020; 32(3): 437-446.e5.
[http://dx.doi.org/10.1016/j.cmet.2020.07.007] [PMID: 32697943]
[20]
Shi Y, Wang Y, Shao C, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ 2020; 27(5): 1451-4.
[http://dx.doi.org/10.1038/s41418-020-0530-3] [PMID: 32205856]
[21]
Bojkova D, Klann K, Koch B, et al. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature 2020; 583(7816): 469-72.
[http://dx.doi.org/10.1038/s41586-020-2332-7] [PMID: 32408336]
[22]
Smallwood HS, Duan S, Morfouace M, et al. Targeting metabolic reprogramming by influenza infection for therapeutic intervention. Cell Rep 2017; 19(8): 1640-53.
[http://dx.doi.org/10.1016/j.celrep.2017.04.039] [PMID: 28538182]
[23]
Zhang W, Wang G, Xu ZG, et al. Lactate is a natural suppressor of RLR signaling by targeting MAVS. Cell 2019; 178(1): 176-189.e15.
[http://dx.doi.org/10.1016/j.cell.2019.05.003] [PMID: 31155231]
[24]
Mills EL, Kelly B, Logan A, et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 2016; 167(2): 457-470.e13.
[http://dx.doi.org/10.1016/j.cell.2016.08.064] [PMID: 27667687]
[25]
Yang X, Qian K. Protein O-GlcNAcylation: emerging mechanisms and functions. Nat Rev Mol Cell Biol 2017; 18(7): 452-65.
[http://dx.doi.org/10.1038/nrm.2017.22] [PMID: 28488703]
[26]
Chen X, Zhou L, Peng N, et al. MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory factor-5 expression and cytokine storm induction. J Biol Chem 2017; 292(52): 21291-303.
[http://dx.doi.org/10.1074/jbc.M117.805937] [PMID: 29046356]
[27]
Stein T, Wollschlegel A, Te H, et al. Interferon regulatory factor 5 and nuclear factor kappa-B exhibit cooperating but also divergent roles in the regulation of pro-inflammatory cytokines important for the development of TH1 and TH17 responses. FEBS J 2018; 285(16): 3097-113.
[http://dx.doi.org/10.1111/febs.14600] [PMID: 29971953]
[28]
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]
[29]
Thaker SK, Ch'ng J, Christofk HR. Viral hijacking of cellular metabolism. BMC Biol 2019; 17(1): 59.
[http://dx.doi.org/10.1186/s12915-019-0678-9] [PMID: 31319842]
[30]
Drucker DJ. Coronavirus infections and type 2 diabetes-shared pathways with therapeutic implications. Endocr Rev 2020; 41(3): bnaa011.
[http://dx.doi.org/10.1210/endrev/bnaa011] [PMID: 32294179]
[31]
Sanchez EL, Lagunoff M. Viral activation of cellular metabolism. Virology 2015; 479-480: 609-18.
[http://dx.doi.org/10.1016/j.virol.2015.02.038] [PMID: 25812764]
[32]
Bojkova D, Costa R, Bechtel M, Ciesek S, Michaelis M, Cinatl J. Targeting pentose phosphate pathway for SARS-CoV-2 therapy. bioRxiv 2020; 257022.
[33]
Prentice E, Jerome WG, Yoshimori T, Mizushima N, Denison MR. Coronavirus replication complex formation utilizes components of cellular autophagy. J Biol Chem 2004; 279(11): 10136-41.
[http://dx.doi.org/10.1074/jbc.M306124200] [PMID: 14699140]
[34]
Wu YH, Tseng CP, Cheng ML, Ho HY, Shih SR, Chiu DT. Glucose-6-phosphate dehydrogenase deficiency enhances human coronavirus 229E infection. J Infect Dis 2008; 197(6): 812-6.
[http://dx.doi.org/10.1086/528377] [PMID: 18269318]
[35]
Ardehali H, Sabbah HN, Burke MA, et al. Targeting myocardial substrate metabolism in heart failure: potential for new therapies. Eur J Heart Fail 2012; 14(2): 120-9.
[http://dx.doi.org/10.1093/eurjhf/hfr173] [PMID: 22253453]
[36]
Chavez PN, Stanley WC, McElfresh TA, Huang H, Sterk JP, Chandler MP. Effect of hyperglycemia and fatty acid oxidation inhibition during aerobic conditions and demand-induced ischemia. Am J Physiol Heart Circ Physiol 2003; 284(5): H1521-7.
[http://dx.doi.org/10.1152/ajpheart.00974.2002] [PMID: 12521928]
[37]
Bharadwaj S, Singh M, Kirtipal N, Kang SG. SARS-CoV-2 and glutamine: SARS-CoV-2 triggered pathogenesis via metabolic reprograming of glutamine in host cells. Front Mol Biosci 2021; 7(462): 627842.
[http://dx.doi.org/10.3389/fmolb.2020.627842] [PMID: 33585567]
[38]
Blanco-Melo D, Nilsson-Payant BE, Liu WC, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 2020; 181(5): 1036-1045.e9.
[http://dx.doi.org/10.1016/j.cell.2020.04.026] [PMID: 32416070]
[39]
Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated type i interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe 2016; 19(2): 181-93.
[http://dx.doi.org/10.1016/j.chom.2016.01.007] [PMID: 26867177]
[40]
Kappler M, Pabst U, Rot S, et al. Normoxic accumulation of HIF1Iα is associated with glutaminolysis. Clin Oral Investig 2017; 21(1): 211-24.
[http://dx.doi.org/10.1007/s00784-016-1780-9] [PMID: 26955835]
[41]
Zhu Y, Li T, Ramos da Silva S, et al. A Critical Role of Glutamine and Asparagine I3-Nitrogen in Nucleotide Biosynthesis in Cancer Cells Hijacked by an Oncogenic Virus. MBio 2017; 8(4): e01179-17.
[http://dx.doi.org/10.1128/mBio.01179-17] [PMID: 28811348]
[42]
Cengiz M, Borku Uysal B, Ikitimur H, et al. Effect of oral l-Glutamine supplementation on Covid-19 treatment. Clin Nutr Exp 2020; 33: 24-31.
[http://dx.doi.org/10.1016/j.yclnex.2020.07.003] [PMID: 32835086]
[43]
Polonikov A. Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in COVID-19 patients. ACS Infect Dis 2020; 6(7): 1558-62.
[http://dx.doi.org/10.1021/acsinfecdis.0c00288] [PMID: 32463221]
[44]
Schwarz KB. Oxidative stress during viral infection: a review. Free Radic Biol Med 1996; 21(5): 641-9.
[http://dx.doi.org/10.1016/0891-5849(96)00131-1] [PMID: 8891667]
[45]
Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013; 1830(5): 3143-53.
[http://dx.doi.org/10.1016/j.bbagen.2012.09.008] [PMID: 22995213]
[46]
Liu Y, Hyde AS, Simpson MA, Barycki JJ. Chapter Two - Emerging Regulatory Paradigms in Glutathione Metabolism. In: Townsend DM, Tew KD, Eds. Advances in Cancer Research 122. Academic Press 2014; pp. 69-101.
[47]
Krishnamoorthy P, Raj AS, Roy S, Kumar NS, Kumar H. Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing. Comput Biol Med 2021; 128: 104123.
[http://dx.doi.org/10.1016/j.compbiomed.2020.104123] [PMID: 33260034]
[48]
Horowitz RI, Freeman PR, Bruzzese J. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Respir Med Case Rep 2020; 30: 101063.
[http://dx.doi.org/10.1016/j.rmcr.2020.101063] [PMID: 32322478]
[49]
Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 2011; 94(3): 847-53.
[http://dx.doi.org/10.3945/ajcn.110.003483] [PMID: 21795440]
[50]
Silvagno FV. COVID-19: Can glutathione (GSH) help to reduce severe symptoms? Available from: https://covid-19.conacyt.mx/jspui/bitstream/1000/2366/1/1101532.pdf
[51]
Santhanam S, Alvarado DM, Ciorba MA. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer. Transl Res 2016; 167(1): 67-79.
[http://dx.doi.org/10.1016/j.trsl.2015.07.003] [PMID: 26297050]
[52]
Mehraj V, Routy JP. Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests. Int J Tryptophan Res 2015; 8: 41-8.
[http://dx.doi.org/10.4137/IJTR.S26862] [PMID: 26309411]
[53]
Raniga K, Liang C. Interferons: Reprogramming the metabolic network against viral infection. Viruses 2018; 10(1): 36.
[http://dx.doi.org/10.3390/v10010036] [PMID: 29342871]
[54]
Belladonna ML, Orabona C. Potential benefits of tryptophan metabolism to the efficacy of tocilizumab in COVID-19. Front Pharmacol 2020; 11(959): 959.
[http://dx.doi.org/10.3389/fphar.2020.00959] [PMID: 32636755]
[55]
Thomas T, Stefanoni D, Reisz JA, et al. COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status. JCI Insight 2020; 5(14): 140327.
[http://dx.doi.org/10.1172/jci.insight.140327] [PMID: 32559180]
[56]
Marchetti C, Swartzwelter B, Gamboni F, et al. OLT1177, a Iβ- sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc Natl Acad Sci USA 2018; 115(7): E1530-9.
[http://dx.doi.org/10.1073/pnas.1716095115] [PMID: 29378952]
[57]
Ballak DB, Brunt VE, Sapinsley ZJ, et al. Short-term interleukin-37 treatment improves vascular endothelial function, endurance exercise capacity, and whole-body glucose metabolism in old mice. Aging Cell 2020; 19(1): e13074.
[http://dx.doi.org/10.1111/acel.13074] [PMID: 31755162]
[58]
Urano T, Castellino FJ, Suzuki Y. Regulation of plasminogen activation on cell surfaces and fibrin. J Thromb Haemost 2018; 16(8): 1487-97.
[http://dx.doi.org/10.1111/jth.14157] [PMID: 29779246]
[59]
Rouse HC, Schlesinger RW. The effects of arginine starvation on macromolecular synthesis in infection with type 2 adenovirus. I. Synthesis and utilization of structural proteins. Virology 1972; 48(2): 463-71.
[http://dx.doi.org/10.1016/0042-6822(72)90057-8] [PMID: 4337030]
[60]
Schierhorn KL, Jolmes F, Bespalowa J, et al. Influenza a virus virulence depends on two amino acids in the n-terminal domain of its ns1 protein to facilitate inhibition of the RNA-dependent protein kinase PKR. J Virol 2017; 91(10): e00198-17.
[http://dx.doi.org/10.1128/JVI.00198-17] [PMID: 28250123]
[61]
Archard LC, Williamson JD. The effect of arginine deprivation on the replication of vaccinia virus. J Gen Virol 1971; 12(3): 249-58.
[http://dx.doi.org/10.1099/0022-1317-12-3-249] [PMID: 4256170]
[62]
Tan KB. The effect of arginine deprivation on DNA, thymidine kinase and RNA polymerase synthesis in simian virus 40-infected monkey kidney cells. Arch Virol 1977; 53(1-2): 133-8.
[http://dx.doi.org/10.1007/BF01314854] [PMID: 192179]
[63]
Saha P, Banerjee AK, Tripathi PP, Srivastava AK, Ray U. A virus that has gone viral: amino acid mutation in S protein of Indian isolate of Coronavirus COVID-19 might impact receptor binding, and thus, infectivity. Biosci Rep 2020; 40(5): BSR20201312.
[http://dx.doi.org/10.1042/BSR20201312] [PMID: 32378705]
[64]
Yang TS, Lu SN, Chao Y, et al. A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients. Br J Cancer 2010; 103(7): 954-60.
[http://dx.doi.org/10.1038/sj.bjc.6605856] [PMID: 20808309]
[65]
Yau T, Cheng PN, Chan P, et al. Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma. Invest New Drugs 2015; 33(2): 496-504.
[http://dx.doi.org/10.1007/s10637-014-0200-8] [PMID: 25666409]
[66]
Vigeland CL, Beggs HS, Collins SL, et al. Inhibition of glutamine metabolism accelerates resolution of acute lung injury. Physiol Rep 2019; 7(5): e14019.
[http://dx.doi.org/10.14814/phy2.14019] [PMID: 30821123]
[67]
Oliveira GP, de Abreu MG, Pelosi P, Rocco PR. Exogenous glutamine in respiratory diseases: myth or reality? Nutrients 2016; 8(2): 76.
[http://dx.doi.org/10.3390/nu8020076] [PMID: 26861387]
[68]
Choi GJ, Kim HM, Kang H. The potential role of dyslipidemia in COVID-19 Severity: an umbrella review of systematic reviews. J Lipid Atheroscler 2020; 9(3): 435-48.
[http://dx.doi.org/10.12997/jla.2020.9.3.435] [PMID: 33024735]
[69]
Xu K, Nagy PD. RNA virus replication depends on enrichment of phosphatidylethanolamine at replication sites in subcellular membranes. Proc Natl Acad Sci USA 2015; 112(14): E1782-91.
[http://dx.doi.org/10.1073/pnas.1418971112] [PMID: 25810252]
[70]
Meher G, Bhattacharjya S, Chakraborty H. Membrane cholesterol modulates oligomeric status and peptide-membrane interaction of severe acute respiratory syndrome coronavirus fusion peptide. J Phys Chem B 2019; 123(50): 10654-62.
[http://dx.doi.org/10.1021/acs.jpcb.9b08455] [PMID: 31743644]
[71]
Fecchi K, Anticoli S, Peruzzu D, et al. Coronavirus interplay with lipid rafts and autophagy unveils promising therapeutic targets. Front Microbiol 2020; 11: 1821.
[http://dx.doi.org/10.3389/fmicb.2020.01821] [PMID: 32849425]
[72]
Wolff G, Melia CE, Snijder EJ, Bárcena M. Double-membrane vesicles as platforms for viral replication. Trends Microbiol 2020; 28(12): 1022-33.
[http://dx.doi.org/10.1016/j.tim.2020.05.009] [PMID: 32536523]
[73]
Heaton NS, Randall G. Multifaceted roles for lipids in viral infection. Trends Microbiol 2011; 19(7): 368-75.
[http://dx.doi.org/10.1016/j.tim.2011.03.007] [PMID: 21530270]
[74]
Douglas I, Evans S, Smeeth L. Effect of statin treatment on short term mortality after pneumonia episode: cohort study. BMJ 2011; 342: d1642.
[http://dx.doi.org/10.1136/bmj.d1642] [PMID: 21471172]
[75]
Papazian L, Roch A, Charles P-E, et al. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA 2013; 310(16): 1692-700.
[http://dx.doi.org/10.1001/jama.2013.280031] [PMID: 24108510]
[76]
Tleyjeh IM, Kashour T, Hakim FA, et al. Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med 2009; 169(18): 1658-67.
[http://dx.doi.org/10.1001/archinternmed.2009.286] [PMID: 19822822]
[77]
Zeiser R. Immune modulatory effects of statins. Immunology 2018; 154(1): 69-75.
[http://dx.doi.org/10.1111/imm.12902] [PMID: 29392731]
[78]
Alleva L, Budd A, Clark I. Minimising influenza disease with fibrates. Int J Infect Dis 2008; 12(1): e176.
[79]
Yuan S, Chu H, Chan JF, et al. SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun 2019; 10(1): 120.
[http://dx.doi.org/10.1038/s41467-018-08015-x] [PMID: 30631056]
[80]
Greseth MD, Traktman P. De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection. PLoS Pathog 2014; 10(3): e1004021.
[http://dx.doi.org/10.1371/journal.ppat.1004021] [PMID: 24651651]
[81]
Lopez LA, Riffle AJ, Pike SL, Gardner D, Hogue BG. Importance of conserved cysteine residues in the coronavirus envelope protein. J Virol 2008; 82(6): 3000-10.
[http://dx.doi.org/10.1128/JVI.01914-07] [PMID: 18184703]
[82]
Lee W, Ahn JH, Park HH, et al. COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm. Signal Transduct Target Ther 2020; 5(1): 186.
[http://dx.doi.org/10.1038/s41392-020-00292-7] [PMID: 32883951]
[83]
Madison BB. Srebp2: A master regulator of sterol and fatty acid synthesis. J Lipid Res 2016; 57(3): 333-5.
[http://dx.doi.org/10.1194/jlr.C066712] [PMID: 26798145]
[84]
Chakinala RC, Khatri A, Gupta K, Koike K, Epelbaum O. Sphingolipids in COPD. Eur Respir Rev 2019; 28(154): 190047.
[PMID: 31694841]
[85]
Hannun YA, Obeid LM. Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol 2018; 19(3): 175-91.
[http://dx.doi.org/10.1038/nrm.2017.107] [PMID: 29165427]
[86]
Lythgoe MP, Middleton P. Ongoing clinical trials for the management of the COVID-19 pandemic. Trends Pharmacol Sci 2020; 41(6): 363-82.
[http://dx.doi.org/10.1016/j.tips.2020.03.006] [PMID: 32291112]
[87]
Huwiler A, Zangemeister-Wittke U. The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives. Pharmacol Ther 2018; 185: 34-49.
[http://dx.doi.org/10.1016/j.pharmthera.2017.11.001] [PMID: 29127024]
[88]
Jiang Y, Liu S, Shen S, Guo H, Huang H, Wei W. Methyl-Iβ-cyclodextrin inhibits EV-D68 virus entry by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts. Antiviral Res 2020; 176: 104752.
[http://dx.doi.org/10.1016/j.antiviral.2020.104752] [PMID: 32101770]
[89]
Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science 2010; 327(5961): 46-50.
[http://dx.doi.org/10.1126/science.1174621] [PMID: 20044567]
[90]
Musarrat F, Chouljenko V, Dahal A, et al. The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections. J Med Virol 2020; 92(10): 2087-95.
[http://dx.doi.org/10.1002/jmv.25985] [PMID: 32374457]
[91]
Niyogi K, Hildreth JE. Characterization of new syncytium-inhibiting monoclonal antibodies implicates lipid rafts in human T-cell leukemia virus type 1 syncytium formation. J Virol 2001; 75(16): 7351-61.
[http://dx.doi.org/10.1128/JVI.75.16.7351-7361.2001] [PMID: 11462007]
[92]
Fang L, Miller YI. Regulation of lipid rafts, angiogenesis and inflammation by AIBP. Curr Opin Lipidol 2019; 30(3): 218-23.
[http://dx.doi.org/10.1097/MOL.0000000000000596] [PMID: 30985364]
[93]
Dubrovsky L, Ward A, Choi SH, et al. Inhibition of HIV replication by apolipoprotein A-I binding protein targeting the lipid rafts. MBio 2020; 11(1): e02956-19.
[http://dx.doi.org/10.1128/mBio.02956-19] [PMID: 31964734]
[94]
Partlow KC, Lanza GM, Wickline SA. Exploiting lipid raft transport with membrane targeted nanoparticles: a strategy for cytosolic drug delivery. Biomaterials 2008; 29(23): 3367-75.
[http://dx.doi.org/10.1016/j.biomaterials.2008.04.030] [PMID: 18485474]
[95]
Shen B, Yi X, Sun Y, et al. Proteomic and metabolomic characterization of COVID-19 patient sera. Cell 2020; 182(1): 59-72.e15.
[http://dx.doi.org/10.1016/j.cell.2020.05.032] [PMID: 32492406]
[96]
Butterworth PJ. Lehninger: principles of biochemistry. (4th ed.). Freeman & Co., New York 2004.
[97]
Noreen S, Maqbool I, Madni A. Dexamethasone: Therapeutic potential, risks, and future projection during COVID-19 pandemic. Eur J Pharmacol 2021; 894: 173854.
[http://dx.doi.org/10.1016/j.ejphar.2021.173854] [PMID: 33428898]
[98]
Schoot TS, Kerckhoffs APM, Hilbrands LB, van Marum RJ. Immunosuppressive drugs and COVID-19: a review. Front Pharmacol 2020; 11: 1333.
[http://dx.doi.org/10.3389/fphar.2020.01333] [PMID: 32982743]
[99]
McKay LICJ. Physiologic and Pharmacologic Effects of Corticosteroids. (6th Edition.). 2003.
[100]
Khiali S, Khani E, Entezari-Maleki T. A comprehensive review of tocilizumab in COVID-19 acute respiratory distress syndrome. J Clin Pharmacol 2020; 60(9): 1131-46.
[http://dx.doi.org/10.1002/jcph.1693] [PMID: 32557541]
[101]
Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a randomized trial. Diabetes Res Clin Pract 2002; 55(3): 209-19.
[http://dx.doi.org/10.1016/S0168-8227(01)00325-4] [PMID: 11850097]
[102]
Valentin-Vega YA, Maclean KH, Tait-Mulder J, et al. Mitochondrial dysfunction in ataxia-telangiectasia. Blood 2012; 119(6): 1490-500.
[http://dx.doi.org/10.1182/blood-2011-08-373639] [PMID: 22144182]
[103]
Ebina-Shibuya R, Namkoong H, Horita N, et al. Hydroxychloroquine and chloroquine for treatment of coronavirus disease 19 (COVID-19): a systematic review and meta-analysis of randomized and non-randomized controlled trials. J Thorac Dis 2021; 13(1): 202-12.
[http://dx.doi.org/10.21037/jtd-20-2022] [PMID: 33569200]
[104]
McGill JB, Johnson M, Hurst S, et al. Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness. Diabetol Metab Syndr 2019; 11: 61.
[http://dx.doi.org/10.1186/s13098-019-0456-4] [PMID: 31384309]
[105]
Poddighe D, Aljofan M. Clinical evidences on the antiviral properties of macrolide antibiotics in the COVID-19 era and beyond. Antivir Chem Chemother 2020; 28: 2040206620961712.
[http://dx.doi.org/10.1177/2040206620961712] [PMID: 32972196]
[106]
Yoo JK, Kim TS, Hufford MM, Braciale TJ. Viral infection of the lung: host response and sequelae. J Allergy Clin Immunol 2013; 132(6): 1263-76.
[http://dx.doi.org/10.1016/j.jaci.2013.06.006] [PMID: 23915713]
[107]
Soman Pillai V, Krishna G, Valiya Veettil M. Nipah Virus: Past Outbreaks and Future Containment. Viruses 2020; 12(4): E465.
[http://dx.doi.org/10.3390/v12040465] [PMID: 32325930]
[108]
Altenburg TM, Rotteveel J, SernA(c) EH, Chinapaw MJ. Effects of Multiple Sedentary Days on Metabolic Risk Factors in Free-Living Conditions: Lessons Learned and Future Recommendations. Front Physiol 2016; 7: 616.
[http://dx.doi.org/10.3389/fphys.2016.00616] [PMID: 28018243]
[109]
Golbidi S, Mesdaghinia A, Laher I. Exercise in the metabolic syndrome. Oxid Med Cell Longev 2012; 2012: 349710.
[http://dx.doi.org/10.1155/2012/349710] [PMID: 22829955]
[110]
Sanchez KK, Chen GY, Schieber AMP, et al. Cooperative Metabolic Adaptations in the Host Can Favor Asymptomatic Infection and Select for Attenuated Virulence in an Enteric Pathogen. Cell 2018; 175(1): 146-158.e15.
[http://dx.doi.org/10.1016/j.cell.2018.07.016] [PMID: 30100182]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy