Cell Rep: How does the new coronavirus escape the cell's antiviral defense

This discovery explains the cellular coup staged by the new coronavirus and how it disrupts normal cellular defenses to hijack human host cells
.

"We found that this virus will attach to and inactivate an important sensor protein called galectin-8 in the host cell, and galectin-8 can protect the host cell from infection
.
By inactivating hemilectin-8, SARS-CoV-2 disarms the cell’s antiviral defense system and allows the virus to take over the host,” said Dr.

In general, a team composed of local, domestic and international collaborators was formed to provide samples for this study, and the results of the study were published in the "Cell Reports" on October 26
.
The co-authors of this research, Dr.

In order to turn the host cell into a virus manufacturing machine, SARS-CoV-2 uses the spike protein surrounding the virus to attach, invade and control the host
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The researchers made an important discovery: Galectin-8 can be attached to the spike protein
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Then, the virus uses a key enzyme of its own-3CL protease-to lock, attach and cut Galectin-8 in half, like a pair of molecular scissors, thereby inactivating Galectin-8

Galectin-8 protects host cells from viruses through a defensive response called "xenophagy": infected cells trap invaders, such as viruses, in small fluid-filled sacs, and then inject them into the sac Destructive molecules kill them
.

Dr.
Pablos said: "The key enzyme makes a single cleavage at a specific molecular site of Galectin-8.
We have accurately identified this through the specialized proteomics technology developed in the overall laboratory
.
" "This cleavage It may weaken the cell’s ability to destroy the virus

Normally, 3CL protease is a key enzyme that helps virus replicate, but the work of the researchers shows that SARS-CoV-2 has cleverly evolved an ability to make its own key enzyme multifunctional and maximize its ability

Researchers used high-resolution microscope images of COVID-19-infected lungs donated by patients to show that the function of galectin-8 in severely infected lung cells was disrupted
.

In addition to galactoside-8, the researchers also discovered about 150 other host cell proteins that are targeted, cut, and inactivated by key virus enzymes
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The inactivation of these host proteins gives the virus the ability to take over human cells

Dr.
Machado said: “How this virus can effectively inhibit the normal ability of host cells by targeting and cutting these basic cellular proteins is incredible
.
” “In our research, we have determined.

When these sites are cut off, the cell is more likely to be occupied by the virus

Overall said: "By understanding how SARS-CoV-2 hinders the host cell's ability to protect itself, and identifying the molecular sites that are cut off to accomplish this task, we can finally understand how the virus hijacks the cell
.
"

"This valuable new knowledge allows us to identify new methods and drugs that target these sites, with the goal of preventing viruses from inactivating key cell functions-all of which are important insights to guide drug development
.
"

Journal Reference :

1. Isabel Pablos, Yoan Machado, Hugo C.
   Ramos de Jesus, Yasir Mohamud, Reinhild Kappelhoff, Cecilia Lindskog, Marli Vlok, Peter A.
   Bell, Georgina S.
   Butler, Peter M.
   Grin, Quynh T.
   Cao, Jenny P.
   Nguyen, Nestor Solis, Srinivas Abbina, Wioletta Rut, John C.
   Vederas, Laszlo Szekely, Attila Szakos, Marcin Drag, Jayachandran N.
   Kizhakkedathu, Karen Mossman, Jeremy A.
   Hirota, Overall Eric Jan, Honglin Luo, Arinjay Banerjee, Christopher M.
   Christopher, Insights INTO COVID.
   19-Mechanistic by The Global Analysis of SARS-CoV of 2-3CLpro Substrate degradome .
   the Cell Reports , 2021; 37 [(.
   4): 109 892 the DOI: 10.
   1016 / j.
   celrep.
   2021.
   109892 MBER.
   1, 2021).