[Science breakthrough] The Nobel Prize female scientist developed a new system tool, focusing on a rarely noticed mutation in Delta, revealing why Delta is so contagious?

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Author: Daisy Guide: On November 4, the research published by the researchers in "Science" shows that the pioneer in the field of CRISPR gene editing and the Nobel Prize winner in chemistry Jennifer Doudna, etc.
The staff developed a powerful tool that can truly understand the current SARS-COV-2 mutation and explore how future mutations will affect the pandemic
.

They focused on a rarely noticed mutation in Delta, R203M, which changes the nucleocapsid protein (N), a protein hidden inside the virus
.

This mutation makes the virus better at producing infectious particles
.

N protein is the central role of virus replication.
In the future, we can consider targeting more nucleocapsid protein to really help control infection and treat patients
.

This new VLP system also makes it possible for researchers who do not have a high level of biological security to more simply study how all four coronavirus structural proteins assemble viruses, help viruses germinate from cells, and invade other cells
.

As the world has realized after paying the price, the Delta variant of the pandemic coronavirus is more than twice as infectious as the previous strain
.

However, what is driving Delta's rapid spread is unclear
.

Now, a new laboratory strategy makes it possible to quickly and safely study the effects of SARS-CoV-2 mutations.
It gives an answer: a rarely noticed mutation in Delta allows the virus to transfer more The gene codes for "squeezed into" the host cell, thereby increasing the chance of each infected cell transmitting the virus to another cell
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On November 4, the discovery published in the journal "Science" was "significant.
" The researchers published an article titled "Why is Delta so infectious? New lab tool spotlights little noticed mutation that speeds viral spread"
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doi: 10.
1126/science.
acx9583 Michael Summers, a structural biologist at the University of Maryland in Baltimore County, said this is not just because it helps explain Delta's ravages
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The new system developed by Jennifer Doudna, a pioneer of CRISPR gene editing and Nobel Prize winner in chemistry at the University of California, Berkeley, Berkeley and colleagues is a powerful tool for understanding current SARS-COV-2 mutations and exploring how future mutations will affect the pandemic
.

"The system she developed allows you to observe any mutations and their effects on key parts of virus replication.
.
.
Now more scientists can study these mutations in a simpler way
.

" The researchers analyzed how mutations in the coronavirus genome are.
Affect its activity, focusing on the spike protein, which nails the surface of the virus so that it can invade human cells
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This is partly because, in addition to deliberate mutation and testing of viruses that require high-level biosafety facilities, the best tool for detecting individual mutations is the so-called "pseudovirus", a structure composed of different viruses (called lentiviruses).
, The coronavirus protein can be expressed on its surface
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However, the lentivirus only expresses spikes and does not express the other three structural proteins of SARS-CoV-2
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Doudna and her team created this new tool by adjusting the laboratory structure called viruslike particles (VLPs)
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VLPs contain all the structural proteins of the virus, but lack the virus genome
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From the outside, SARS-CoV-2 VLP looks exactly like a mature virus
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It can bind to and invade cells in the laboratory
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But because it is stripped of the virus's RNA genome, it cannot hijack the cell to replicate and rush out of the host cell to infect more cells
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Charles Rice, a molecular virologist at Rockefeller University, said: “This is a one-way ticket
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It will not spread
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” Doudna and her colleagues, including co-senior author, virologist, and director of the Gladstone Institute for Virology, Melanie Ott, said A new innovation has been added to the VLP system
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They inserted fragments of mRNA to make cells invaded by VLPs glow
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After being infected with VLPs, the brighter the cell luminescence, the more mRNA successfully delivered by the VLPs
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Next, the researchers fine-tuned the VLP protein with different mutations
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One of them is R203M, a mutation found in Delta that changes the nucleocapsid protein (N), a protein hidden inside the virus that can package its RNA genome
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The N protein is a central role in virus replication, and its role includes stabilizing and releasing the genetic material of the virus
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It also contains a mutation hotspot: in most of the samples studied, there is a mutated 7 amino acid fragment in every SARS-CoV-2 variant of interest or concern
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R203M is a mutation in this hot spot
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Doudna said the study "revealed a surprise
.
"
According to the intensity of the VLP luminescence, compared with the original virus, "an amino acid change found in the nucleocapsid protein of Delta caused the particles to produce 10 times more mRNA than the original virus!" found in Alpha and Gamma variants Cells infected with VLPs carrying N mutations emit 7.
5 times and 4.
2 times, respectively
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Next, the scientists tested a real coronavirus under appropriate laboratory biosafety conditions, which was designed to contain the R203M mutation
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In the laboratory, after the mutant virus invades the lung cells, the infectious virus produced by the mutant virus is 51 times that of the original SARS-CoV-2 strain
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In a person infected with a coronavirus, only a small portion of the virus particles produced by one cell can infect another cell, partly because many virus particles lack part or all of the viral RNA genome
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Therefore, mutations that allow the virus to more efficiently put RNA into the host cell can increase the number of infectious particles produced
.

Abdullah Syed, a biomedical engineer at the Gladstone Institute of Data Science and Biotechnology and one of the first authors of the paper, said: "This mutation found in Delta.
.
.
makes the virus better at making infectious particles, so it spreads.
Faster
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" Shan Lu, a cell biologist at the University of California, San Diego, who studies N protein, said that this discovery has implications for treatment
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"This field can consider targeting more nucleocapsid proteins to really help control infections and treat patients
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"Researchers are now trying to understand how Delta's R203M mutation and other mutations in N improve the assembly of virus particles and the delivery of their mRNA to host cells
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They will detect whether it is related to host proteins
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If so, use drugs.
Targeting may be an effective way to prevent the spread of Delta
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Scientists are also excited about the new VLP system, which will enable researchers without a high level of biosafety to study how all four coronavirus structural proteins assemble viruses , Helping viruses germinate from cells and invade other cells
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Jasmine Cubuk, a biochemist and biophysicist who studies the SARS-CoV-2 N protein at Washington University in St.
Louis, called it "a fascinating and very powerful tool
.
"
Rice said that the new VLPs are a model system and may not always imitate the real thing
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Researchers still need to study real viruses in advanced biosafety laboratories
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"In the final analysis, if you really want to understand what these mutations are How to affect the basic virus replication process, you must implant (a mutation) in the virus and study it
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"But he praised this new tool: "It does provide an excellent system to study the assembly of coronaviruses, and find drugs and inhibitors that interfere with these processes
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"Reference: https:// Note: This article aims to Introduce medical research progress and cannot be used as a reference for treatment plan
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If you need health guidance, please go to a regular hospital
.

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