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Article ; Online: SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control.

Naidu, Sreus A G / Clemens, Roger A / Naidu, A Satyanarayan

2022 Volume 20, Issue 2, Page(s) 312–371

Abstract: Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. ...

Abstract	Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19.
MeSH term(s)	Humans ; Iron/metabolism ; Ferroptosis/physiology ; Anticoagulants/pharmacology ; Anticoagulants/therapeutic use ; COVID-19 ; SARS-CoV-2/metabolism ; Oxidation-Reduction ; Iron Chelating Agents ; Iron Overload/drug therapy ; Homeostasis ; Cytokines/metabolism
Chemical Substances	Iron (E1UOL152H7) ; Anticoagulants ; Iron Chelating Agents ; Cytokines
Language	English
Publishing date	2022-05-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2022.2075072
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Article ; Online: Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against RNA-Dependent RNA Polymerase Complex (nsp7/nsp8/nsp12) of SARS-CoV-2

Naidu, Sreus A. G. / Mustafa, Ghulam / Clemens, Roger A. / Naidu, A. Satyanarayan

Journal of Dietary Supplements. 2023 Mar. 4, v. 20, no. 2 p.254-283

2023

Abstract: The emergence of fast-spreading SARS-CoV-2 mutants has sparked a new phase of COVID-19 pandemic. There is a dire necessity for antivirals targeting highly conserved genomic domains on SARS-CoV-2 that are less prone to mutation. The nsp12, also known as ... ...

Abstract	The emergence of fast-spreading SARS-CoV-2 mutants has sparked a new phase of COVID-19 pandemic. There is a dire necessity for antivirals targeting highly conserved genomic domains on SARS-CoV-2 that are less prone to mutation. The nsp12, also known as the RNA-dependent RNA-polymerase (RdRp), the core component of ‘SARS-CoV-2 replication-transcription complex’, is a potential well-conserved druggable antiviral target. Several FDA-approved RdRp ‘nucleotide analog inhibitors (NAIs)’ such as remdesivir, have been repurposed to treat COVID-19 infections. The NAIs target RdRp protein translation and competitively block the nucleotide insertion into the RNA chain, resulting in the inhibition of viral replication. However, the replication proofreading function of nsp14-ExoN could provide resistance to SARS-CoV-2 against many NAIs. Conversely, the ‘non-nucleoside analog inhibitors (NNAIs)’ bind to allosteric sites on viral polymerase surface, change the redox state; thereby, exert antiviral activity by altering interactions between the enzyme substrate and active core catalytic site of the RdRp. NNAIs neither require metabolic activation (unlike NAIs) nor compete with intracellular pool of nucleotide triphosphates (NTPs) for anti-RdRp activity. The NNAIs from phytonutrient origin are potential antiviral candidates compared to their synthetic counterparts. Several in-silico studies reported the antiviral spectrum of natural phytonutrient-NNAIs such as Suramin, Silibinin (flavonolignan), Theaflavin (tea polyphenol), Baicalein (5,6,7-trihydroxyflavone), Corilagin (gallotannin), Hesperidin (citrus bioflavonoid), Lycorine (pyrrolidine alkaloid), with superior redox characteristics (free binding energy, hydrogen-bonds, etc.) than antiviral drugs (i.e. remdesivir, favipiravir). These phytonutrient-NNAIs also exert anti-inflammatory, antioxidant, immunomodulatory and cardioprotective functions, with multifunctional therapeutic benefits in the clinical management of COVID-19.
Keywords	COVID-19 infection ; Citrus ; RNA ; RNA-directed RNA polymerase ; Severe acute respiratory syndrome coronavirus 2 ; active sites ; antioxidants ; antiviral agents ; antiviral properties ; computer simulation ; energy ; enzyme substrates ; genomics ; hesperidin ; hydrogen bonding ; lycorine ; mutation ; phytonutrients ; suramin ; tea ; theaflavins ; therapeutics ; virus replication ; Antiviral ; COVID-19 ; Non-nucleoside analog inhibitors (NNAIs) ; nsp14-ExoN ; Redox ; Remdesivir ; RNA-dependent RNA polymerase (RdRp) ; SARS-CoV-2
Language	English
Dates of publication	2023-0304
Size	p. 254-283.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2021.2006387
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control

Naidu, Sreus A.G. / Clemens, Roger A. / Naidu, A. Satyanarayan

Journal of Dietary Supplements. 2023 Mar. 4, v. 20, no. 2 p.312-371

2023

Abstract: Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. Phase-I – Hypoxia correlates with reduced O₂ transport by erythrocytes, overexpression of HIF- ... ...

Abstract	Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. Phase-I – Hypoxia correlates with reduced O₂ transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). Phase-II – Hyperferritinemia results from an increased iron overload, which triggers a fulminant proinflammatory response – the acute cytokine release syndrome (CRS). Elevated cytokine levels (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 patients. Phase-III – Thromboembolism is consequential to erythrocyte dysfunction with heme release, increased prothrombin time and elevated D-dimers, cumulatively linked to severe coagulopathies with life-threatening outcomes such as ARDS, and multi-organ failure. Taken together, Fe-R-H dysregulation is implicated in every symptomatic phase of COVID-19. Fe-R-H regulators such as lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, reduce oxidative stress, and improve host defense by optimizing iron metabolism. Due to its pivotal role in ‘cytokine storm’, ferroptosis is a potential intervention target. Ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, quercetin, and melatonin could prevent mitochondrial lipid peroxidation, up-regulate antioxidant/GSH levels and abrogate iron overload-induced apoptosis through activation of Nrf2 and HO-1 signaling pathways. Iron chelators such as heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid could protect against ferroptosis and restore mitochondrial function, iron-redox potential, and rebalance Fe-R-H status. Therefore, Fe-R-H restoration is a host biomarker-driven potential combat strategy for an effective clinical and post-recovery management of COVID-19.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antioxidants ; apoptosis ; caffeic acid ; curcumin ; deferoxamine ; energy metabolism ; erythrocytes ; erythropoietin ; ferritin ; ferroptosis ; heme ; heparin ; hepcidin ; homeostasis ; hypoxia ; inflammation ; interleukin-6 ; iron ; iron absorption ; iron overload ; lactoferrin ; lipid peroxidation ; melatonin ; mitochondria ; oxidative stress ; phytic acid ; prothrombin ; quercetin ; COVID-19 ; ferroptosis inhibitors ; Fe-R-H regulators ; host metabolic reprogramming (HMR) ; iron chelators ; iron-redox homeostasis (Fe-R-H)
Language	English
Dates of publication	2023-0304
Size	p. 312-371.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2022.2075072
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against

Naidu, Sreus A G / Mustafa, Ghulam / Clemens, Roger A / Naidu, A Satyanarayan

Journal of dietary supplements

2021 Volume 20, Issue 2, Page(s) 254–283

Abstract	The emergence of fast-spreading SARS-CoV-2 mutants has sparked a new phase of COVID-19 pandemic. There is a dire necessity for antivirals targeting highly conserved genomic domains on SARS-CoV-2 that are less prone to mutation. The
MeSH term(s)	Humans ; RNA-Dependent RNA Polymerase/chemistry ; RNA-Dependent RNA Polymerase/genetics ; RNA-Dependent RNA Polymerase/metabolism ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Pandemics ; COVID-19 ; RNA ; Nucleotides ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Antiviral Agents/chemistry
Chemical Substances	RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; RNA (63231-63-0) ; Nucleotides ; Antiviral Agents
Language	English
Publishing date	2021-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2021.2006387
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Phytonutrient Inhibitors of SARS-CoV-2/NSP5-Encoded Main Protease (Mᵖʳᵒ) Autocleavage Enzyme Critical for COVID-19 Pathogenesis

Naidu, Sreus A. G. / Tripathi, Yamini B. / Shree, Priya / Clemens, Roger A. / Naidu, A. Satyanarayan

Journal of Dietary Supplements. 2023 Mar. 4, v. 20, no. 2 p.284-311

2023

Abstract: The genomic reshuffling, mutagenicity, and high transmission rate of the SARS-CoV-2 pathogen highlights an urgent need for effective antiviral interventions for COVID-19 control. Targeting the highly conserved viral genes and/or gene-encoded viral ... ...

Abstract	The genomic reshuffling, mutagenicity, and high transmission rate of the SARS-CoV-2 pathogen highlights an urgent need for effective antiviral interventions for COVID-19 control. Targeting the highly conserved viral genes and/or gene-encoded viral proteins such as main proteinase (Mᵖʳᵒ), RNA-dependent RNA polymerase (RdRp) and helicases are plausible antiviral approaches to prevent replication and propagation of the SARS-CoV-2 infection. Coronaviruses (CoVs) are prone to extensive mutagenesis; however, any genetic alteration to its highly conserved Mᵖʳᵒ enzyme is often detrimental to the viral pathogen. Therefore, inhibitors that target the Mᵖʳᵒ enzyme could reduce the risk of mutation-mediated drug resistance and provide effective antiviral protection. Several existing antiviral drugs and dietary bioactives are currently repurposed to treat COVID-19. Dietary bioactives from three ayurvedic medicinal herbs, 18 β-glycyrrhetinic acid (ΔG = 8.86 kcal/mol), Solanocapsine (ΔG = 8.59 kcal/mol), and Vasicoline (ΔG = 7.34 kcal/mol), showed high-affinity binding to Mᵖʳᵒ enzyme than the native N3 inhibitor (ΔG = 5.41 kcal/mol). Flavonoids strongly inhibited SARS-CoV-2 Mᵖʳᵒ with comparable or higher potency than the antiviral drug, remdesivir. Several tannin hydrolysates avidly bound to the receptor-binding domain and catalytic dyad (His₄₁ and Cys₁₄₅) of SARS‐CoV‐2 Mᵖʳᵒ through H-bonding forces. Quercetin binding to Mᵖʳᵒ altered the thermostability of the viral protein through redox-based mechanism and inhibited the viral enzymatic activity. Interaction of quercetin-derivatives with the Mᵖʳᵒ seem to be influenced by the 7-OH group and the acetoxylation of sugar moiety on the ligand molecule. Based on pharmacokinetic and ADMET profiles, several phytonutrients could serve as a promising redox nutraceutical for COVID-19 management.
Keywords	COVID-19 infection ; RNA-directed RNA polymerase ; Severe acute respiratory syndrome coronavirus 2 ; antiviral agents ; dietary supplements ; drug resistance ; enzyme activity ; genomics ; hydrogen bonding ; ligands ; moieties ; mutagenesis ; mutagenicity ; pathogenesis ; pathogens ; pharmacokinetics ; phytonutrients ; proteinases ; quercetin ; risk reduction ; sugars ; thermal stability ; Antiviral ; Ayurvedic Medicine ; COVID-19 ; Mpro ; Redox nutraceutical ; SARS-CoV-2
Language	English
Dates of publication	2023-0304
Size	p. 284-311.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2021.2006388
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.

Naidu, A Satyanarayan / Wang, Chin-Kun / Rao, Pingfan / Mancini, Fabrizio / Clemens, Roger A / Wirakartakusumah, Aman / Chiu, Hui-Fang / Yen, Chi-Hua / Porretta, Sebastiano / Mathai, Issac / Naidu, Sreus A G

NPJ science of food

2024 Volume 8, Issue 1, Page(s) 19

Abstract: SARS-CoV-2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29. ...

Abstract	SARS-CoV-2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus-host protein-protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia ('cytokine storm'), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25-70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new 'onset' clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.
Language	English
Publishing date	2024-03-30
Publishing country	England
Document type	Journal Article ; Review
ISSN	2396-8370
ISSN (online)	2396-8370
DOI	10.1038/s41538-024-00261-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Phytonutrient Inhibitors of SARS-CoV-2/NSP5-Encoded Main Protease (M

Naidu, Sreus A G / Tripathi, Yamini B / Shree, Priya / Clemens, Roger A / Naidu, A Satyanarayan

Journal of dietary supplements

2021 Volume 20, Issue 2, Page(s) 284–311

Abstract	The genomic reshuffling, mutagenicity, and high transmission rate of the SARS-CoV-2 pathogen highlights an urgent need for effective antiviral interventions for COVID-19 control. Targeting the highly conserved viral genes and/or gene-encoded viral proteins such as main proteinase (M
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2/metabolism ; Quercetin/pharmacology ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Antiviral Agents/chemistry ; Peptide Hydrolases/pharmacology ; Phytochemicals/pharmacology
Chemical Substances	Quercetin (9IKM0I5T1E) ; Antiviral Agents ; Peptide Hydrolases (EC 3.4.-) ; Phytochemicals
Language	English
Publishing date	2021-11-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2021.2006388
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19.

Naidu, Sreus A G / Wallace, Taylor C / Davies, Kelvin J A / Naidu, A Satyanarayan

Journal of dietary supplements

2021 Volume 20, Issue 2, Page(s) 218–253

Abstract: Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly ... ...

Abstract	Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier
MeSH term(s)	Humans ; Blood-Brain Barrier/metabolism ; Parkinson Disease ; Lactoferrin/metabolism ; Lactoferrin/therapeutic use ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Alzheimer Disease/drug therapy ; Mental Health ; Endothelial Cells/metabolism ; COVID-19 ; SARS-CoV-2/metabolism ; Iron/metabolism ; Iron/therapeutic use ; Neurodegenerative Diseases/drug therapy ; Oxidation-Reduction
Chemical Substances	Lactoferrin (EC 3.4.21.-) ; Neuroprotective Agents ; Iron (E1UOL152H7)
Language	English
Publishing date	2021-05-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2021.1922567
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: COVID-19 during Pregnancy and Postpartum

Naidu, Sreus A. G. / Clemens, Roger A. / Pressman, Peter / Zaigham, Mehreen / Davies, Kelvin J. A. / Naidu, A. Satyanarayan

Journal of dietary supplements. 2022 Jan. 2, v. 19, no. 1

II) Antiviral Spectrum of Maternal Lactoferrin in Fetal and Neonatal Defense

2022

Abstract: As the COVID-19 pandemic intensified the global health crisis, the containment of SARS-CoV-2 infection in pregnancies, and the inherent risk of vertical transmission of virus from mother-to-fetus (or neonate) poses a major concern. Most COVID-19- ... ...

Abstract	As the COVID-19 pandemic intensified the global health crisis, the containment of SARS-CoV-2 infection in pregnancies, and the inherent risk of vertical transmission of virus from mother-to-fetus (or neonate) poses a major concern. Most COVID-19-Pregnancy patients showed mild to moderate COVID-19 pneumonia with no pregnancy loss and no congenital transmission of the virus; however, an increase in hypoxia-induced preterm deliveries was apparent. Also, the breastmilk of several mothers with COVID-19 tested negative for the virus. Taken together, the natural barrier function during pregnancy and postpartum seems to deter the SARS-CoV-2 transmission from mother-to-child. This clinical observation warrants to explore the maternal-fetal interface and identify the innate defense factors for prevention and control of COVID-19-Pregnancy. Lactoferrin (LF) is a potent antiviral iron-binding protein present in the maternal-fetal interface. In concert with immune co-factors, maternal-LF modulates chemokine release and lymphocyte migration and amplify host defense during pregnancy. LF levels during pregnancy may resolve hypertension via down-regulation of ACE2; consequently, may limit the membrane receptor access to SARS-CoV-2 for cellular entry. Furthermore, an LF-derived peptide (LRPVAA) has been shown to block ACE receptor activity in vitro. LF may also reduce viral docking and entry into host cells and limit the early phase of COVID-19 infection. An in-depth understanding of LF and other soluble mammalian milk-derived innate antiviral factors may provide insights to reduce co-morbidities and vertical transmission of SARS-CoV-2 infection and may lead to the development of effective nutraceutical supplements.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; breast milk ; chemokines ; dietary supplements ; hypertension ; lactoferrin ; mammals ; neonates ; pneumonia ; pregnancy ; risk ; viruses
Language	English
Dates of publication	2022-0102
Size	p. 78-114.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2020.1834047
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19

Naidu, Sreus A. G. / Wallace, Taylor C. / Davies, Kelvin J. A. / Naidu, A. Satyanarayan

Journal of Dietary Supplements. 2021 Apr. 28, v. 20, no. 2 p.218-253

2021

Abstract	Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier via receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Lactoferrin receptors are additionally present on glioma cells, brain micro-vessels, and neurons. As a regulator of neuro-redox, microglial lactoferrin is critical for protection/repair of neurons and healthy brain function. Iron imbalance and oxidative stress are common among patients with neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, dementia, depression, and multiple sclerosis. As an endogenous iron-chelator, lactoferrin prevents iron accumulation and dopamine depletion in Parkinson’s disease patients. Oral lactoferrin supplementation could modulate the p-Akt/PTEN pathway, reduce Aβ deposition, and ameliorate cognitive decline in Alzheimer’s disease. Novel lactoferrin-based nano-therapeutics have emerged as effective drug-delivery systems for clinical management of neurodegenerative disorders. Recent emergence of the Coronavirus disease-2019 (COVID-19) pandemic, initially considered a respiratory illness, demonstrated a broader virulence spectrum with the ability to cross the blood-brain barrier and inflict a plethora of neuropathological manifestations in the brain – the Neuro-COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are widely reported in Parkinson’s disease, Alzheimer’s disease, dementia, and multiple sclerosis patients with aggravated clinical outcomes. Lactoferrin, credited with several neuroprotective benefits in the brain could serve as a potential adjuvant in the clinical management of Neuro-COVID-19.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; adjuvants ; blood-brain barrier ; brain ; cognitive disorders ; dementia ; dopamine ; glioma ; lactoferrin ; mental health ; neuroglia ; oxidative stress ; pandemic ; physiological transport ; respiratory tract diseases ; sclerosis ; virulence ; Alzheimer’s disease ; brain tumor ; COVID-19 ; neurological symptoms ; Neuro-COVID-19 ; Parkinson’s Disease ; Redox ; SARS-CoV-2
Language	English
Dates of publication	2021-0428
Size	p. 218-253.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2021.1922567
Database	NAL-Catalogue (AGRICOLA)

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