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COVID-19 News - Omicron Variant - Unique Insertion Mutation- ins214EPE   Jun 16, 2023  8 months, 1 week, 2 days, 20 hours, 21 minutes ago

BREAKING! Scientists Discover That SARS-CoV-2 Omicron Variant Harbors A Unique Insertion Mutation, ins214EPE Of Unknown Putative Genomic Origin!

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BREAKING! Scientists Discover That SARS-CoV-2 Omicron Variant Harbors A Unique Insertion Mutation, ins214EPE Of Unknown Putative Genomic Origin!
COVID-19 News - Omicron Variant - Unique Insertion Mutation- ins214EPE   Jun 16, 2023  8 months, 1 week, 2 days, 20 hours, 21 minutes ago
Fact That Omicron Contains A Unique Insertion Mutation Of Putative Viral Or Human Genomic Origin Raises Questions About Its Origins!

COVID-19 News: In a groundbreaking discovery, scientists have unveiled the distinctive genetic makeup of the Omicron variant of the SARS-CoV-2 virus. This variant, which has caused widespread concern due to its potential impact on public health, carries a novel insertion mutation labeled ins214EPE. Researchers from nference Cambridge, Massachusetts-USA, nference labs in Bengaluru-India and and nference in Toronto-Canada collaborated on this study.

To fully understand the uniqueness of the Omicron variant, scientists compared its mutational profile to those of other notable variants such as Alpha, Beta, Gamma, and Delta. They also analyzed data from 5.4 million SARS-CoV-2 genomes, encompassing 1523 lineages. Out of the 37 mutations observed in Omicron's Spike protein, 26 were found to be unique to this variant. While substitution and deletion mutations have been seen in previous lineages, the insertion mutation ins214EPE appears exclusively in Omicron.
This discovery raises important questions about the origin and significance of ins214EPE. One possibility is that the inserted nucleotide sequence was acquired through template switching, a process involving the genetic material of other viruses infecting the same host cells as SARS-CoV-2 or even the human transcriptome of cells infected with SARS-CoV-2.
Co-infections of COVID-19 patients with seasonal coronaviruses, such as HCoV-229E, have been reported, and genomic data analysis reveals similarities between the nucleotide sequence encoding ins214EPE and the Spike protein of HCoV-229E.
This suggests that the Omicron insertion may have evolved within an individual simultaneously infected with multiple viruses.
Past studies and COVID-19 News had also speculated on the origins of the Omicron variant. >
The researchers emphasize the need to investigate the function of the Omicron insertion and whether it exploits human host cells as an "evolutionary sandbox" for viral genomic interplay.

Venn diagram depicting the overlap of lineage specific spike mutations in the SARS-CoV-2 variants of concern. The unique key mutations observed in the spike protein for each of the variants are highlighted (spheres) on the homo-trimeric Spike protein of SARS-CoV-2. The B.1.1.529 (Omicron) variant has the highest number (26) of unique mutations in the spike protein from this perspective, making its emergence a “step function” in evolution of SARS-CoV-2 strains.
Understanding this mechanism is crucial for deciphering Omicron's clinical behavior, its potential resistance to existing vaccines, and the possibility of future variants with increased virulence.
In the context of SARS-CoV-2 evolution, mutations have played a significant role in shaping the behavior of different variants. Missense mutations in the Spike protein have altered its affinity for the ACE2 receptor, while deletions have affected the effectiveness of neutralizing antibodies. Insertion mutations, however, have been less prevalent in the evolutionary history of SARS-CoV-2.
The exception is the "PRRA" insertion, which introduced a polybasic FURIN cleavage site in the original strain, significantly impacting viral behavior.

 a. Potential mechanism of template switching leading to the generation of the ins214EPE in Omicron. Schematic representations show human body and human cells being infected by Omicron’s predecessor variant (blue) and a human coronavirus HCoV-229E (orange). The box shows the potential steps in the template switching involving the genomic RNA (+) of Omicron’s predecessor variant and the anti-genomic RNA (-) of HCoV-229E. The steps involving the anti-genomic RNA are shown inside a grey box.
b. Comparison of nucleotides corresponding to the Omicron insert with a homologous match from HCoV 229E. Sequence alignment of the genomic regions corresponding to Omicron Spike and HCoV229E Spike are shown

Analyzing the mutational landscape of Omicron in comparison to other variants sheds light on the unique features of this variant and helps prepare for future challenges.
While the origin of the ins214EPE insertion remains enigmatic, the study highlights potential scenarios, including template switching during viral co-infections or the utilization of prevalent templates within the human genome.
As the world grapples with the ongoing pandemic and strives to vaccinate global populations, monitoring the emergence of new variants is crucial. The mutational landscape of SARS-CoV-2 is constantly evolving, and early detection of variants of concern is vital for effective containment strategies. Therefore, further genomic sequencing and the development of a robust "variant warning system" are essential for staying one step ahead of the ever-changing virus.
The study findings were published on a preprint server and are currently being peer reviewed.
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