Abstract; On November 24, 2021, the World Health Organization (WHO) received the first report of this mutant strain from South Africa and listed it as a Variant of Concern (VOC) 2 days later.
The mutant was first reported to the World Health Organization (WHO) in South Africa on November 24, 2021, and was listed as a Variant of Concern (VOC) two days later. In reality, the Omicron subtype BA.2 quickly replaced BA.1 as the main prevalent strain. The ongoing Omicron outbreak in Hong Kong, China is of this subtype.
However, the latest reports from the UK are that new coronaviruses are recombining, particularly BA.1 and BA.2, and one type has been named XE. There is already data that XE has a significantly shorter infection time and may spread 10% faster than the mainstream Omicron, meaning it may be more infectious than BA.2!
On March 28, a research team from the University of Hong Kong posted on the preprint website that they had detected BA.1/BA.2 recombinant mutant (XE) infections in passengers arriving in Hong Kong in February 2022, after excluding co-infection and sample contamination.
A total of 2 patients are reported in this report.
Patient 1 had a sore throat and cough in late January 2022, whereas patient 2 was asymptomatic. Both patients received two doses of the new crown pneumonia vaccine (Pfizer), and both patients received the second dose in November 2021 and June 2021, respectively.
No similar BA.1/BA.2 recombinant sequences were found in GISIAD and Genbank, suggesting that this is a new recombinant. The BA.1 region of this recombinant virus is genetically similar to BA.1 sequences found in Europe and the United States, while its BA.2 region is identical to BA.2 sequences from several continents.
As can be seen from the above graph, these two patients possess both BA.1 and BA.2 partial mutations, with relatively more BA.2. Among them, in the S protein, it is completely BA.2 mutation, which means it has similar infectivity to BA.2, and the UK study suggests that it is 9.8% higher than BA.2, which is possible. And in ORF1ab, completely inherited from BA.1. while ORF3a,M,N,ORF6 are derived from BA.2. ORF3a and signal blocking protein ORF6 suggest that its immune escape and viral replication are similar to BA.2.
The 29 proteins of SARS-CoV-2 and their functions
According to the investigators, the high transmission rate of Omicron has led to the spread of its BA.1 and BA.2 subtypes in multiple regions, which has provided the conditions for the emergence of recombinants. Although the XE variant infections detected in this study were sporadic cases, the potential impact of this recombinant should not be underestimated. This calls for long-term genomic surveillance of SARS-CoV-2 on a global scale.
Although most of the people infected with the new variant of Omicron XE are currently from Europe, given that the virus is more transmissible and most infections are asymptomatic, it should not be taken lightly and there is a high probability that the virus will spread widely around the world with the movement of people, which means that it may cause a new wave of new crown epidemics and pose difficulties for global prevention efforts.
Functional description of the genome-associated proteins of the new coronavirus, the 29 proteins of SARS-CoV-2
1、16 kinds of protein chain-ORF1ab
The first viral protein produced inside cells infected by SARS-CoV-2 is actually a protein chain of 16 proteins bound together. Two of these proteins act like scissors to release the proteins from the protein chain.
This protein slows down the production of the infected cells' own proteins. This destructive behavior forces the cell to produce more viral proteins.
It is not yet possible to determine the functionality of NSP2. The proteins to which it attaches may provide some clues, two of which contribute to the movement of endosomes.
Unlabeling and Cleavage Protein-NSP3
NSP3 is a protein with two important functions, one of which is to cleave other viral proteins in order to perform their respective functions. It also alters many of the proteins of infected cells. Normally healthy cells tag old proteins for degradation. But SARS-CoV-2 virus can remove these tags, altering the balance of proteins and reducing the cell's ability to resist the virus.
Vesicle manufacturing protein-NSP4
NSP4 binds to other proteins and helps form fluid-filled bubble structures within infected cells, and this is where some of the new viruses are built.
This protein frees most other NSP proteins from the protein chain.
Liquid Bubble Factory-NSP6
Work with NSP3 and NSP4 to build the bubble structure for producing viruses.
Copy Assistant - NSP7 and NSP8
These two proteins can help NSP12 generate new copies of the RNA genome for the assembly of new viruses.
The protein seeps into the nucleus of infected cells through tiny channels, and it may be able to influence the movement of molecules in and out of the nucleus - but for what purpose is unknown.
Human cells have antiviral proteins that recognize viral RNA and degrade it. nSP10 can bind to nsp16 to camouflage the genome of the virus so that it will not be attacked.
This protein assists in the replication of the viral genome. Researchers have found in other coronaviruses that the antiviral remdesivir interferes with NSP12. Another sequence, NSP11, overlaps with a portion of the RNA that encodes NSP12. But it is not clear whether the tiny protein encoded by this gene is functional.
RNA Unraveling Protein-NSP13
The viral RNA gets tangled up. Researchers speculate that NSP13 can unwind the entangled RNA strands for replication or protein translation.
Virus Proofreader - NSP14
NSP12 assists in the replication of the viral genome and sometimes makes errors. nsp14 corrects these errors.
The researchers speculate that this protein will shred the remaining viral RNA to evade the body's antiviral defense response.
NSP16 together with NSP10 can hide the genome of the virus from the proteins that cut viral RNA.
Stinger proteins are proteins that form the outer layer of the coronavirus and protect one of the four structural proteins S, E, M and N of the internal RNA. By forming a trimer, the S protein forms a distinct spine on the surface of the virus. A portion of the spines can extend and attach to the ACE2 protein (shown in yellow), and the virus can then invade the cell. 12 bases are inserted into the gene for the spine protein of SARS-CoV-2: ccucggcgggca. This mutation may help the spines bind more tightly to human cells. Many research teams are currently designing drugs to prevent the spike-in protein from attaching to human cells.
The SARS-CoV-2 genome also encodes a set of so-called "auxiliary proteins". The ORF3a protein punches holes in the membranes of infected cells, making it easier for the virus to escape.
Envelope protein is a structural protein. Once the virus is inside the cell, it locks onto the protein, which helps to open and close the genome of the infected cell.
Another structural protein that forms the outer shell of the virus.
6、Signal blocking protein-ORF6
The protein prevents infected cells from sending signals to the immune system. It also blocks some of the cell's own antiviral proteins.
7, Viral escape protein-ORF7a
When replicating new viruses try to escape the cell, the cell can capture them with a protein called tetherin. Some studies have shown that ORF7a reduces the expression of tetherin in infected cells, which allows more viruses to escape. The researchers also found that this protein can trigger infected cells to commit suicide, causing damage to infected tissues.
8. Mystery protein-ORF8
The gene for this protein in SARS-CoV-2 is significantly different from other coronaviruses. Researchers are exploring its role.
9、Nuclear capsid protein-N
The N protein protects the viral RNA and keeps it stable inside the virus. Many N proteins are linked together in a long helix to wrap the RNA.
10. ORF9b and ORF9c
The RNA fragments encoding proteins ORF9b and ORF9c overlap. ORF9b blocks interferon and resists the body's viral defenses, but the role of ORF9c is not yet clear.
A close relative of SARS-CoV-2 does not have a gene for this tiny helper protein, and its use is unclear.
12, RNA group tail of SARS-CoV-2
The genome of the coronavirus ends with a small segment of RNA, which terminates protein translation, and then with a repetitive aaaaaaaaaaaaaaa sequence.