A novel mutation in SARS-CoV-2 may explain the high pathogenicity of COVID-19

Researchers in South Korea and the United States have announced a new gene variant that shows the progression of active mutations in drugs that cause severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – coronavirus disease 2019 (COVID-19) Identified.

Two of the mutations occurred in the receptor-binding domain of the virus Spike protein – The structure used by the virus to bind to the host cell.

The third mutation occurred in a subdomain of the spike protein close to the established one D614G A variant known to enhance the infectivity and spread of the virus. The SARS-CoV-2 spike D614G mutant has been the predominant strain worldwide since the end of March.

“This particular sequence data showed active progression of SARS-CoV-2 by mutation of RBD in S. [spike] “This study, which has a novel mutation in an important RBD of the S gene, may explain the high pathogenicity of SARS-CoV-2,” the team wrote.

Researchers have found that sequence information for such novel mutations is essential for the development of recombinant SARS-CoV-2 spike antigens that may help advance strategies for a wide range of possible mutations. It states.

Studies recently published in the journal Immune networkWas conducted by Kim Soo-Hyun of the Founding University and others, and collaborators of various other institutions in South Korea, the University of Colorado, and the National Jewish Health Center in Denver, USA.

Seven coronaviruses infect humans

SARS-CoV-2 is one of seven Coronavirus It infects humans, including the beta coronavirus SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV), and occurred between 2002, 2003, and 2012, respectively.

However, SARS-CoV-2 is particularly infectious, causing unprecedented medical, social and economic disruption in many parts of the world.

“Currently SARS-CoV-2 is highly contagious and has caused the worst pandemic on the planet in the last 100 years,” said Kim et al.

Importance of S gene and spike protein

The SARS-CoV-2 S gene encodes the surface structure of the viral envelope called spikes. Glycoprotein.. The spike protein is cleaved by the host cell protease into two domains, the S1 subunit and the S2 subunit.

The S1 subunit contains a receptor binding domain (RBD) that recognizes and interacts with the host cell receptor angiotensin converting enzyme 2. This is followed by conformational changes in the S2 subunit that allow membrane fusion and delivery of the viral genome to the cell. ..

“A more accurate understanding of how SARS-CoV-2 invades host cells is a priority, as interruption of this invasion can reduce SARS-CoV2 replication and spread,” the team wrote. I am.

Studies have confirmed that a single point mutation in the S gene (D614G) enhances the infectivity of SARS-CoV-2 compared to wild-type virus. However, Kim et al. State that the importance of this mutation is unclear because it is located in the S2 subunit rather than in the RBD.

The SARS-CoV-2 genome shares approximately 80% identity with the SARS-CoV-1 genome, and SARS-CoV-1 also uses ACE2 to invade target cells.

Nevertheless, SARS-CoV-2 is much more infectious and contagious than SARS-CoV-1, despite similar genomic sequences and shared host cell receptors.

A recent study comparing the cleavage sites of SARS-CoV-1 and SARS-CoV-2 found differences in the cleavage of the S1 and S2 subunits. It states that Kim and his colleagues may be explaining the difference in infectivity.

What did your current research find?

Nasopharyngeal swabs collected from Korean COVID-19 patients were tested for SARS-CoV-2 infection. The S gene was isolated using four positive samples and the spiked RBD was investigated.

The N-terminal region of the S gene was translated into an amino acid sequence and entered into the NCBI database (National Center for Biotechnology Information).

This revealed two novel mutations (G504D / V524D) in the important RBD of the S gene.

The third mutation (P579L) was identified in subdomain 2, which is close to the D614G mutation, but has no specific known function, the researchers say.

“Therefore, we need to investigate the function of different domains of the spike gene to explain the importance of SARS-CoV2 pathogenic mutations,” they write.

Kim et al. State that these novel mutations in the important RBD of the S gene indicate the progression of SARS-CoV-2 in Korean COVID-19 patients.

“Sequential information for new mutations is important for the development of recombinant SARS-CoV2 spike antigens, which may be needed to improve and advance strategies for a wide range of possible SARS-CoV-2 mutations. There is sex, “the team concludes.