The Francis Crick Institute
ijms-23-04126-v3 (1).pdf (3.38 MB)

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

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journal contribution
posted on 2022-04-20, 08:39 authored by Jason Iles, Raminta Zmuidinaite, Christoph Sadée, Anna Gardiner, Jonathan Lacey, Stephen Harding, Jernej Ule, Debra Roblett, Jonathan Heeney, Helen Baxendale, Ray K Iles
The immune response to SARS‐CoV‐2 infection requires antibody recognition of the spike protein. In a study designed to examine the molecular features of anti‐spike and anti‐nucleocapsid antibodies, patient plasma proteins binding to pre‐fusion stabilised complete spike and nucleocap-sid proteins were isolated and analysed by matrix‐assisted laser desorption ionisation–time of flight (MALDI‐ToF) mass spectrometry. Amongst the immunoglobulins, a high affinity for human serum albumin was evident in the anti‐spike preparations. Careful mass comparison revealed the preferential capture of advanced glycation end product (AGE) forms of glycated human serum albumin by the pre‐fusion spike protein. The ability of bacteria and viruses to surround themselves with serum proteins is a recognised immune evasion and pathogenic process. The preference of SARS‐ CoV‐2 for AGE forms of glycated serum albumin may in part explain the severity and pathology of acute respiratory distress and the bias towards the elderly and those with (pre)diabetic and athero-sclerotic/metabolic disease.