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Researchers identify novel SARS-CoV-2 mutants that are not registered in the genomic sequence database

A team of scientists at the University of California, Santa Cruz recently announced a novel variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that may be prevalent in at least 20 states in the United States (B. 1.x) has been identified. And 6 countries in the world. The mutations found in this mutant are also present in other known mutants of concern (VOCs). Importantly, the sequence of B.1.x was rejected by the automated sequence checking tool used in the published genomic sequence database due to the presence of large deletion mutations.The study is currently available at bioRxiv* Preprint server.

Background

Whole-genome sequencing of SARS-CoV-2 is one of the traditional methods for tracking viral evolution. Continuous sequencing of the viral genome is particularly important for identifying mutations that emerge under positive selection and playing an important role in improving viral compatibility, such as increased infectivity and avoidance of host immunity. It is important. In other words, early detection of new viral variants by genomic sequencing is essential for understanding strain-specific clinical features and developing strain-specific diagnostics and therapeutic and prophylactic interventions.

In the late pandemic of coronavirus disease (COVID-19) in 2019, several new SARS-CoV-2 mutants were identified, some showing significantly higher infectivity and antigenic escape potential. These variants have serious impacts on public health reactions and are therefore designated as Concern Variants (VOCs). The presence of multiple spike mutations is most common in various VOCs, including the British variant (strain: B.1.1.7), the South African variant (strain: B.1.351), and the Brazilian variant (strain: P). This is a general feature. 1).

In the current report, scientists present SARS-CoV-2 genomic sequencing data from ongoing research.

Study design

Scientists have analyzed high-quality SARS-CoV-2 sequences from 339 samples in Santa Cruz County, California. Approximately 58% of these sequences were from the B.1.427 and B.1.429 strains first identified in California. In addition, two of the tested sequences were associated with the B.1.1.7 strain (UK variant).

Important findings

Scientists have identified novel variants of SARS-CoV-2 in eight samples by sequencing the genome. Due to their relevance to the B.1 strain, they temporarily named the variant B.1.x. Upon further analysis, they observed that the novel mutants shared some mutations with UK mutants and other known VOCs. Specifically, the variant showed several spike mutations, including S494P, N501Y, D614G, P681H, K854N, and E1111K. Of these mutations, N501Y is known to increase the binding affinity between the spike receptor binding domain (RBD) and angiotensin converting enzyme 2 (ACE2). Similarly, the D614G mutation, which was present in the globally predominant mutant of SARS-CoV-2 in 2020, is known to increase viral infectivity. In addition, the B.1.x variant shows one nucleocapsid mutation (N: M234I), which is predicted to increase protein stability.

Regarding the transmission dynamics of B.1.x, scientists have noticed that the shape of the frequency increases over time (January).<1%から3月中旬までの> Ten%). However, no variants could be detected in the samples collected at the end of March. Further investigation revealed that the increased frequency of B.1.x was primarily due to increased local infections rather than multiple virus introduction events. Overall, these observations suggest that the number of B.1.x cases may increase over time. By analyzing samples published from different parts of the United States, they found that variants exist in at least 20 states throughout the United States.

Phylogenetic distribution of 339 samples from the SARS-CoV-2 sequence in Santa Cruz County and 1000 samples from elsewhere. This tree is created via the UShER web portal of hgPhyloPace (https://genome.ucsc.edu/cgi-bin/hgPhyloPlace). To generate it, 339 genomes from Santa Cruz County samples were added to the global phylogeny of over 1 million SARS CoV-2 genomes, then pruned and randomly selected with the Santa Cruz genome. It retained only the other 1000 genomes. Visualized the tree using the Auspice.us platform. 339 samples from Santa Cruz County are colored red, 8 samples representing B.1.x are highlighted in gold, and the remaining 1000 samples are colored by the Nextstrain Clade. Note that the size of the clade reflects both penetration and local sampling efforts and is not trying to correct either effect.

Phylogenetic distribution of 339 samples from the SARS-CoV-2 sequence in Santa Cruz County and 1000 samples from elsewhere. This tree is created through the UShER web portal of hgPhyloPace (https://genome.ucsc.edu/cgi-bin/hgPhyloPlace). To generate it, 339 genomes from Santa Cruz County samples were added to the global phylogeny of over 1 million SARS CoV-2 genomes, then pruned and randomly selected with the Santa Cruz genome. It retained only the other 1000 genomes. Visualized the tree using the Auspice.us platform. 339 samples from Santa Cruz County are colored red, 8 samples representing B.1.x are highlighted in gold, and the remaining 1000 samples are colored by the Nextstrain Clade. Note that the size of the clade reflects both penetration and local sampling efforts and is not trying to correct either effect.

Most interestingly, scientists have observed that the mutant contains a 35 bp deletion, causing a frameshift and premature stop codon in open reading frame 8 (ORF8). These features are also present in the B.1.1.7 strain due to nonsense mutations. Such similarities between B.1.x and B.1.1.7 variants suggest that ORF8 inactivation may be associated with viral evolution.

When scientists were submitting sequences to a public database, both GISAID and GenBank first ran all eight genomes of the B.1.x variant due to a large deletion mutation in ORF8. I noticed that I refused. This indicates that due to technical issues associated with automated sequence quality control tools, sequences belonging to the B.1.x lineage are rarely reported by these databases. To overcome such submission errors, scientists are proposing the use of the UShER program to quickly deploy new sequences to existing phylogeny. This allows confirmation between closely related sequences with new mutations during batch or individual sequence transmissions.

Importance of research

This study identifies a new SARS-CoV-2 variant that shares genomic similarity with other known VOCs such as B.1.1.7. Based on the findings, scientists are calling for rapid monitoring to understand the exact infectious dynamics and clinical significance associated with the new SARS-CoV-2 mutant.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.

Researchers identify novel SARS-CoV-2 mutants that are not registered in the genomic sequence database

Source link Researchers identify novel SARS-CoV-2 mutants that are not registered in the genomic sequence database

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