​Nature Liu Yang et al. Reveal the N501Y mutation of the new coronavirus spike protein enhances virus infection and spread

On November 24, 2021, Dr.
Yang Liu from The University of Texas Medical Branch (UTMB) and his colleagues published a titled The N501Y spike substitution enhances SARS-CoV-2 infection and Transmission's article
.

In this study, the human primary respiratory epithelial cell system and a hamster animal model were used to evaluate all amino acid point mutations in the spike protein of the new coronavirus Alpha mutant strain (B.
1.
1.
7 strain); the result was found , The replacement of amino acid No.
501 from asparagine to tyrosine significantly improves the binding ability of the viral spike protein and human ACE2 receptor, which is a decisive factor in the improvement of the ability of new coronavirus infection and transmission
.

This study explains the reason why the Alpha strain of the new coronavirus has spread rapidly around the world from 2020 to 2021
.

The Delta mutant strain (B.
1.
617.
2 strain) that has recently appeared and accelerated its spread has also begun to appear with N501Y mutations, suggesting that the new coronavirus still has the possibility of intensifying the epidemic
.

The new coronavirus (SARS-CoV-2) has spread globally on a large scale since 2019 and continues to this day; so far, it has caused nearly 260 million infections and 5.
2 million deaths, seriously threatening human health and public health security
.

With the epidemic of the new coronavirus, a variety of new mutant viruses have appeared in the United Kingdom, South Africa, Brazil, India and other places.
There are many evidences that these mutant viruses have enhanced infection ability, accelerated transmission speed, and immune escape.
They quickly spread to all parts of the world, causing great social panic
.

Research on the genetic evolution of viruses can determine the genetic determinants that trigger the spread of new mutant viruses and reveal the molecular mechanisms that lead to increased virus infection capabilities; thereby helping us to better warn and prevent future outbreaks of potential mutant strains
.

Beginning in 2020, the Alpha strain of the new crown virus first appeared in the UK, and it has spread rapidly across the world
.

Infectious competition assays on animal models such as hamsters have shown that the spike protein of the Alpha strain is the core protein that causes the increase in its ability to infect and spread
.

The spike protein is an important structural protein that mediates the binding of the new coronavirus to the host cell and the invasion of the virus; its mutation will affect the virus' host range, tissue tropism, transmission capacity and pathogenicity
.

Compared with the earlier and popular D614G mutant strain (USA-WA1/2020 strain with D614G mutation), the Alpha strain has an additional 8 conservative amino acid mutations on the spike protein
.

Researchers constructed and rescued recombinant new coronaviruses containing these 8 amino acid single-point mutations on the backbone of the D614G strain, and used infection competition experiments to simulate the real competitive evolution process of viruses in nature; they compared these amino acid point mutations respectively.
In the wild-type D614G virus infection and transmission ability changes in hamster animal models
.

Experimental results show that only the N501Y mutation can stabilize the upper respiratory tract, trachea and lungs of hamsters to enhance virus infection, and reproduce the phenotype that the intact spike protein enhances the ability of virus infection and transmission
.

Subsequently, the researchers verified that the spike protein N501Y mutation enhances the ability of the virus to infect on a variety of cell lines and human respiratory epithelial cell systems
.

The N501Y mutation is located in the Receptor Binding Domain of the virus, and its change is likely to result in a change in the ability of the virus to bind to the receptor
.

Human angiotensin-converting enzyme 2 (ACE2) has been shown to be the most important receptor for mediating neocoronavirus infection in animals
.

Therefore, the researchers compared the binding ability of the RBD protein of the N501Y mutant virus/wild-type virus and the human ACE2 receptor
.

It was found that the binding capacity of N501Y mutant virus and human ACE2 receptor is hundreds of times that of wild-type virus
.

The results of this series of experiments show that the N501Y mutation of the spike protein of the new coronavirus greatly enhances the ability of the virus to bind to the ACE2 receptor, making it easier for the virus to enter the cell; after the virus spreads, it can be in the human upper respiratory tract more quickly Establish a stable early infection; thus, the Alpha strain wins the competition with the wild-type virus and becomes the most widespread strain globally
.

Fortunately, in other studies by Dr.
Yang Liu (NEJM, Liu et al.
, 2021a; NEJM, Liu et al.
, 2021b), it is proved that the Alpha strain has not acquired the ability to escape human immune recognition during its evolution.
; People who have received the new crown vaccine have a higher resistance to the Alpha strain than the wild strain
.

Vaccination on a global scale is of great significance to control the spread of the Alpha strain
.

Professor Scott Weaver and Professor Shi Peiyong from the University of Texas Medical Branch (UTMB) are the co-corresponding authors of this article
.

Dr.
Yang Liu, Dr.
Jianying Liu, and Dr.
Kenneth Plante from the University of Texas Medical Branch (UTMB) are the co-first authors of the article
.

The first author of the study, Dr.
Yang Liu, was the recipient of the Wu Rui Scholarship in 2018.
He is currently a distinguished researcher at the Shenzhen Bay Laboratory of Infectious Diseases.
His research direction is the genetic evolution of new and recurring viral infectious diseases; the research team is recruiting research assistants And post-doctorate (http:// and welcome young talents who are interested to join
.

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.