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Source: Research News  Oct 08, 2020  3 years, 6 months, 1 week, 3 days, 1 hour, 17 minutes ago

BREAKING! Research News: Oxford Study Discovers That SARS-CoV-2 Evades Host Immune Responses By Proteolytic Cleavage Of Nucleocapsid

BREAKING! Research News: Oxford Study Discovers That SARS-CoV-2 Evades Host Immune Responses By Proteolytic Cleavage Of Nucleocapsid
Source: Research News  Oct 08, 2020  3 years, 6 months, 1 week, 3 days, 1 hour, 17 minutes ago
Research News: Scientist from the Physical and Theoretical Chemistry Laboratory at the University of Oxford have made a startling discovery as to yet another one of the many modes that the SARS-CoV-2 coronavirus is able to evade human host immune responses once it is inside the host cells and replicating.


The study team discovered that that the nucleocapsid protein of SARS-CoV-2 coronavirus undergoes autoproteolysis, and that the resulting products can escape the host immune responses and facilitate viral proliferation.
 
The research findings are published on a preprint server and have yet to be peer reviewed. https://www.biorxiv.org/content/10.1101/2020.10.06.328112v1
or https://www.biorxiv.org/content/10.1101/2020.10.06.328112v1.full.pdf
 
Studies have shown that the genome of SARS-CoV-2 encodes 25 non-structural proteins and 4 structural proteins, including the spike, membrane, nucleocapsid, and envelop proteins. Besides spike protein, the nucleocapsid is the most abundant protein that encapsulates the viral RNA.
 
The SARS-CoV-2 nucleocapsid (N) protein is the most immunogenic of the structural proteins and plays essential roles in several stages of the virus lifecycle including viral replication/proliferation, virion assembly, host cell cycle regulation, and host immune system evasion.
 
The nucleocapsid (N) protein is comprised of two major structural domains: the RNA binding domain, which interacts with viral and host RNA, and the oligomerization domain which assembles to form the viral core.
 
Interestingly, studies have found that host adaptive immune responses to nucleocapsid is more sensitive than the spike protein, which makes nucleocapsid an important therapeutic target.
 
In the context of many other viruses, many in vitro studies have shown that molecules targeting nucleocapsid proteins are effective in inhibiting viral replication, transcription, and virion assembly.
 
Considering the critical significance of nucleocapsid protein in anti-viral drug development, the study team aimed at deciphering the involvement of nucleocapsid protein in the SARS-CoV-2 lifecycle.
 
It must be noted that there are two major structural domains of the nucleocapsid protein: the RNA binding domain and the oligomerization domain, separated by an extended, flexible linker region.
 
Importantly, the RNA binding domain interacts with both host and viral RNA, whereas the oligomerization domain forms the viral core.
 
The study team utilizing native mass spectrometry, observed and found that that the dimers of full-length nucleocapsid protein interact with RNA, indicating that dimers, and not monomers, are the functional unit of ribonucleoprotein assembly.
 
Significantly the team observed that nucleocapsid protein dimers preferentially bind RNA through the GGG motif, which is known to form stem-loop structures.
 
Surprisingly, the researchers observed that