It seems that the receptor (orange) of human cells and the “receptor binding domain (RBD)” of the spike protein are linked. The red part is the mutation of “E484K} (provided by Rikkyo University, Yuji Mochizuki Laboratory)
COVID-19: Variant has strong cell binding: ‘Fugaku’ analyzes
Supercomputer ‘Fugaku’ analyzed:
Simulation using the RIKEN supercomputer “Fugaku”.
Infectivity of mutant strains:
A mutant strain of the new coronavirus
The power to bind to human cells
I found a mechanism that is stronger than conventional stocks.
A research team at Rikkyo University announced on April 28th.
Elucidation of the mechanism of infection:
“What kind of effect does mutation have on the mechanism of infection?” Was elucidated at the molecular level.
It is expected to be useful for research on vaccines and therapeutic agents in the future.
Compare variant infectivity:
UK stocks 1.03 times,
South African and Brazilian stocks 1.20 times,
Peplomer:
Peplomer is made up of 1300 amino acids.
The part called the “receptor binding domain (RBD)” that is part of the peaplomer.
Infection begins with “the binding of RBD to receptors on the cell surface.”
Mutation increases infectivity:
“Mutations that replace some of the amino acids in RBD” have occurred in British, South African, and Brazilian strains.
This seems to be the cause of the increased infectivity.
Research team analyzed:
Analyze the magnitude and type of binding force “between RBD and all amino acids of the receptor”.
“How they change due to mutation” is reproduced by simulation.
Simulation analysis result:
The results were integrated and the “strength of RBD and receptor binding” was evaluated.
Compared to conventional stocks
UK stocks 1.03 times,
South African and Brazilian stocks 1.20 times,
It was found that the binding force of the receptor was strengthened.
Due to mutation, plus and minus are reversed:
For example, the South African strain, which is said to have strong infectivity, has a mutation called “E484K”.
this is,
It is shown that the 484th amino acid “glutamic acid (E)” of the spike protein is replaced with “lysine (K)”.
Glutamic acid is negatively charged. On the other hand, ricin is a plus.
Originally, “the force that was stably bound to the positively charged amino acid on the cell side” weakened, and on the contrary, it began to repel.
On the other hand, “a phenomenon in which the binding force is strengthened by attracting to the negative part on the cell side” has occurred.
Future research:
This time, we analyzed the interaction with cell receptors.
In the simulation with the mutant strain model, the result that the binding force is strengthened was obtained.
It will lead to research to prepare for future mutation risk.
Professor Yuji Mochizuki of Rikkyo University:
Taking advantage of the overwhelming computing power of ‘Fugaku’
You can now analyze interactions,
It has become possible to make predictions that cannot be obtained in experiments.
In the future, it can be applied to research to investigate the effects of vaccines and drugs.
Sankei News
https://www.sankei.com/life/news/210428/lif2104280030-n1.html