Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 Prion-Like Domains in Spike Proteins Enable Higher Affinity to ACE2

Version 1 : Received: 27 March 2020 / Approved: 29 March 2020 / Online: 29 March 2020 (06:16:20 CEST)

A peer-reviewed article of this Preprint also exists.

Tetz, G.; Tetz, V. Prion-like Domains in Spike Protein of SARS-CoV-2 Differ across Its Variants and Enable Changes in Affinity to ACE2. Microorganisms 2022, 10, 280. https://doi.org/10.3390/microorganisms10020280 Tetz, G.; Tetz, V. Prion-like Domains in Spike Protein of SARS-CoV-2 Differ across Its Variants and Enable Changes in Affinity to ACE2. Microorganisms 2022, 10, 280. https://doi.org/10.3390/microorganisms10020280

Abstract

Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prion-like domains are critical for virulence and the development of therapeutic targets; however, the prion-like domains in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in the SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike protein, since SARS-CoV-2 was the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of the spike protein is particularly interesting, since although the SARS-CoV-2 and SARS-CoV S proteins share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. Finally, we identified prion-like domains in the α1 helix of the ACE2 receptor that interact with the viral receptor-binding domain of SARS-CoV-2. Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interact with RBD have important functional roles in viral adhesion and entry.

Keywords

COVID-19; SARS; SARS-CoV-2 Prion-like domain

Subject

Medicine and Pharmacology, Medicine and Pharmacology

Comments (0)

Comment 1
Received: 10 August 2021
Commenter: Erik Veldman
The commenter has declared there is no conflict of interests.
Comment: Dear sir(s),

First of all, my name is Erik Veldman. I live in Switzerland and recently came across your paper on the issue of the COVID-19 vaccine and its "possible effects" on the brain. I am writing to ask whether on not this paper was peer-reviewed and was approved fellow scientists. And also to find out whether or not it is wise to have a person vaccinated who is suffering from the Moya-Moya disease (and another with moderate hydrocephalus yet not vaccinated). I read your article with interest since my sister-in-law has the Moya-Moya disease and well, under pressure of her environment, she has taken the Moderna vaccine. And currently she is showing signs of forgetfulness, but that is not really rare with her. She was operated on when she was younger, but now she's in her late 50's so we don't really know what the effects will be with the vaccine.

Knowing that you are not her doctor or specialists in the Moya-Moya disease, I found your article very interesting and also scary to read since my sister-in-law has this disease. I thank you for any information you can provide on whether or not it will cause damage to her.

With my sincerest regards,

Erik J. Veldman
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Comment 2
Received: 6 December 2021
Commenter: Rongomai Bailey
The commenter has declared there is no conflict of interests.
Comment: Hi there,

This is really important research. Does it suggest that the spike protein may be able to cause a prion disease?

Is there any other research out there on this subject?

thank you for your time?
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