SARS-CoV-2 Spike Protein Binding of Glycated Serum Albumin—Its Potential Role in the Pathogenesis of the COVID-19 Clinical Syndromes and Bias towards Individuals with Pre-Diabetes/Type 2 Diabetes and Metabolic Diseases

Iles, Jason K.; Zmuidinaite, Raminta; Sadée, Christoph; Gardiner, Anna; Lacey, Jonathan; Harding, Stephen; Ule, Jernej; Roblett, Debra; Heeney, Jonathan L.; Baxendale, Helen; Iles, Ray K.

doi:10.3390/ijms23084126

Cited by 18 publications

(27 citation statements)

References 40 publications

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“…However, unlike the pattern of the antibody binding to a solid-phase antigen seen in IgG1, the prefusion stabilized spike protein also appeared to have a non-specific binding affinity for IgG3, selectively binding IgG3 from the plasma of sero-negative HCWs, as well as that of patients and sero-positive HCWs. This was similar to our previously reported affinity of the prefusion spike protein for HSA, but of a higher mass form due to advanced glycation end product (AGE) modification (i.e., glycated albumin) [ 15 ].…”

Section: Discussionsupporting

confidence: 91%

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Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding—Who Is Binding Who and Why?

Iles

Zmuidinaite

Sadée

et al. 2022

IJMS

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The involvement of immunoglobulin (Ig) G3 in the humoral immune response to SARS-CoV-2 infection has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) in COVID-19. The exact molecular mechanism is unknown, but it is thought to involve this IgG subtype’s differential ability to fix, complement and stimulate cytokine release. We examined the binding of convalescent patient antibodies to immobilized nucleocapsids and spike proteins by matrix-assisted laser desorption/ionization–time of flight (MALDI-ToF) mass spectrometry. IgG3 was a major immunoglobulin found in all samples. Differential analysis of the spectral signatures found for the nucleocapsid versus the spike protein demonstrated that the predominant humoral immune response to the nucleocapsid was IgG3, whilst for the spike protein it was IgG1. However, the spike protein displayed a strong affinity for IgG3 itself, as it would bind from control plasma samples, as well as from those previously infected with SARS-CoV-2, similar to the way protein G binds IgG1. Furthermore, detailed spectral analysis indicated that a mass shift consistent with hyper-glycosylation or glycation was a characteristic of the IgG3 captured by the spike protein.

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Section: Discussionsupporting

confidence: 91%

“…To minimize these problems, as well as individual operator variability in the efficiency of target binding protein recoveries, the Crick automated magnetic rack system was employed. This has previously been described in full [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding—Who Is Binding Who and Why?

Iles

Zmuidinaite

Sadée

et al. 2022

IJMS

Self Cite

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“…Albumin serves as a major anti-inflammatory agent in our bodies [ 19 , 20 ], and one of its properties that has been less discussed in the literature is its anti-oxidative and anti-thrombotic activity [ 21 , 22 ]. It may also exhibit antiviral properties, as recent studies have revealed that albumin specifically binds the SARS-CoV-2 spike protein S1 subunit [ 23 ]. Human serum albumin (HSA) comprises the largest thiol pool in plasma and thus determines the plasma redox status [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences

Wybranowski

Napiórkowska

Bosek

et al. 2022

IJMS

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Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result in elevated levels of advanced oxidation protein products (AOPPs) and advanced lipoxidation end-products (ALEs) that trigger oxidative bursts of neutrophils and thus participate in cytokine storms, accelerating endothelial lung cell injury, leading to respiratory distress. In this study, sixty-six hospitalized COVID-19 patients with respiratory symptoms were studied. AOPPs-HSA was produced in vitro by treating human serum albumin (HSA) with chloramine T. The interaction of malondialdehyde with HSA was studied using time-resolved fluorescence spectroscopy. The findings revealed a significantly elevated level of AOPPs in COVID-19 pneumonia patients on admission to the hospital and one week later as long as they were in the acute phase of infection when compared with values recorded for the same patients 6- and 12-months post-infection. Significant negative correlations of albumin and positive correlations of AOPPs with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, and radiological scores of computed tomography (HRCT), were observed. The AOPPs/albumin ratio was found to be strongly correlated with D-dimers. We suggest that oxidized albumin could be involved in COVID-19 pathophysiology. Some possible clinical consequences of the modification of albumin are also discussed.

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Section: Generation Of Vulnerabilities That Spread Systemically To Ca...mentioning

confidence: 99%

“…Glycated albumin has a greater affinity for virions than albumin and the ability of bacteria and viruses to surround themselves with serum proteins is a recognised immune evasion and pathogenic process [26]. SARS-CoV-2 spike binding protein binds to glycated serum albumin [26]. Long term binding of virions in interstitial spaces would slow the flow and isolate COVID-19 virions shielded by albumin for many weeks and may be an explanation for Long-COVID-19.…”

Section: Generation Of Vulnerabilities That Spread Systemically To Ca...mentioning

confidence: 99%

Appropriate Human Serum Albumin Fluid Therapy and the Alleviation COVID-19 Vulnerabilities; An Explanation of the HSA Lymphatic Nutrient Pump

Johnson¹,

Polese²,

Johnson³

et al. 2022

Preprint

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COVID-19 and long COVID-19 vulnerabilities may be caused indirectly by albumin binding deficiency (ABD) which can be corrected by the correct administration of human serum albumin (HSA). The liver is the primary site of nutrient regulation and fluid volume maintenance, control of both is by changes to albumin concentration. In healthy subjects the HSA lymphatic nutrient pump (HSALNP) ensures continual pumping of nutrients from the liver are appropriately distributed to organs. Nutrients are delivered to cells according to the availability of binding to HSA. The HSALNP therefore maintains the correct nutrients and colloidal pressure balance in all tissues independently. In unhealthy tissues, following COVID-19 infection, the passage of HSA/nutrients through the interstitial spaces and lymph will be impeded. Fluid therapy into the periphery leads to dilution of essential nutrients attached to the protein-carriers such as albumin. The levels of albumin being charged by the liver with nutrients is critical in maintaining immune stability by maintaining nutrient support and colloidal pressure of cellular structures. The site of HSA binding by the liver is of great importance and direct infusion of albumin into the Hepatic Portal Vein is the most appropriate method of maintaining colloid pressure and cellular nutrient levels.

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SARS-CoV-2 Spike Protein Binding of Glycated Serum Albumin—Its Potential Role in the Pathogenesis of the COVID-19 Clinical Syndromes and Bias towards Individuals with Pre-Diabetes/Type 2 Diabetes and Metabolic Diseases

Cited by 18 publications

References 40 publications

Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding—Who Is Binding Who and Why?

Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding—Who Is Binding Who and Why?

Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences

Appropriate Human Serum Albumin Fluid Therapy and the Alleviation COVID-19 Vulnerabilities; An Explanation of the HSA Lymphatic Nutrient Pump

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