A comprehensive mini-review on amyloidogenesis of different SARS-CoV-2 proteins and its effect on amyloid formation in various host proteins

Abstract

Amyloidogenesis is the inherent ability of proteins to change their conformation from native state to cross β-sheet rich fibrillar structures called amyloids which result in a wide range of diseases like Parkinson's disease, Alzheimer’s disease, Finnish familial amyloidosis, ATTR amyloidosis, British and Danish dementia, etc. COVID-19, on the other hand is seen to have many similarities in symptoms with other amyloidogenic diseases and the overlap of these morbidities and symptoms led to the proposition whether SARS-CoV-2 proteins are undergoing amyloidogenesis and whether it is resulting in or aggravating amyloidogenesis of any human host protein. Thus the SARS-CoV-2 proteins in infected cells, i.e., Spike (S) protein, Nucleocapsid (N) protein, and Envelope (E) protein were tested via different machinery and amyloidogenesis in them were proven. In this review, we will analyze the pathway of amyloid formation in S-protein, N-protein, E-protein along with the effect that SARS-CoV-2 is creating on various host proteins leading to the unexpected onset of many morbidities like COVID-induced Acute Respiratory Distress Syndrome (ARDS), Parkinsonism in young COVID patients, formation of fibrin microthrombi in heart, etc., and their future implications.

Introduction

Protein folding and binding provide the basis for life on earth. The native 3D structure of a protein is necessary for its biological function (Perozzo et al. 2004). Among many protein folding models such as diffusion-collision, nucleation-condensation, jigsaw puzzle, hydrophobic collapse and stoichiometry models, the “folding funnel” model based on the free energy landscape theory has now been most widely accepted (Shu-Qun Liu et al. 2021; Smith et al. 1979; Koike and Katsuno 2020; Driggin et al. 2020).

At present, worldwide 97 COVID vaccines are in the pipeline, 37 vaccines have been approved/authorized and being used all over the world (Craven 2022; Jeyanathan et al. 2020; Flaxman et al. 2020). Most of the authorized and develo** vaccines use either S-protein or N-protein of SARS-CoV-2 as the main antigen, which means apart from the viral infection, we are being medically incorporated with the amyloidogenic viral proteins in the ever-increasing doses of vaccination. Thus, it is of utmost importance to study the side-effects of vaccination using the amyloidogenic viral proteins, as being done in the case of SARS-CoV-2 to prevent the onset of amyloidosis related cardiopathy and neuropathy including neurodegenerative diseases like Alzheimer's disease and Parkinson's disease; seeds of which are being borne in our system from a young age due to COVID-related amyloidogenesis. Summarized data on the amyloidogenic proteins of COVID-19, their mechanism of action and future implications is provided on Table 2.

Table 2 Future implications of the interactions established between COVID-19 and amyloidogeneis

Conclusion

COVID-19 has been the greatest bane to our existence in recent times and teamed up with the age-old machinery of amyloidogenesis, it is resulting in aggravated complications and morbidities in critical amyloidogenic diseases like ATTR (transthyretin amyloidosis). S-protein and N-protein amyloidogenesis, resulting due to endoproteolysis and proteastasis of cellular αS protein, respectively, may lead to aggregation and amyloid formation that can cause neurodegenerative and other amyloidogenic cardiac and neural complications in future. Along with this, the side effects of COVID-19 vaccination using these very proteins as their main antigen needs to be studied properly to prevent the onset of amyloidogenesis related pathological conditions in individuals post SARS-CoV-2 infection, and aggravation of common morbidities between COVID-19 and critical amyloidogenic diseases like ATTR.