Scientists report a complex mutation pattern for Omicron BA.2.

Evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, has diminished Effectiveness of Vaccines available. These vaccines Spike protein Of the ancestor SARS-CoV-2 that appeared in Wuhan, China in 2019.

Scientists have classified the newly emerging SARS-CoV-2 mutants as Variant of Concern (VOC), Variant of Concern (VOI), and Monitored Mutant (VBM). Researchers have said that for nsp14, a virus with a calibration mechanism, the high rate of mutation is surprising.

Background

Studies have shown that SARS-CoV-2 VOCs are highly contagious, toxic, and can evade immune defenses induced by COVID-19 vaccination or spontaneous infection. To date, five VOCs have been identified: alpha, beta, gamma, delta, and omicron.

In most countries around the world, the Omicron subspecies has replaced the Delta subspecies and is the predominantly circulating strain. The World Health Organization has classified the Omicron variants into strain B.1.1.529 and subspecies BA.1, BA.1.1, BA.2, and BA.3. Currently, Omicron’s BA.2 substrain is predominantly circulating in many parts of the world. Previous studies have shown that this strain is more infectious than BA.1. Therefore, it is essential to understand why this strain is more contagious than other Omicron substrains.

the study

Recently, scientists have studied the mutation profile of BA.2 and analyzed the results based on their interaction with receptors and / or monoclonal antibodies.This study is available at International Journal of Molecular Science..

To study the mutation profile of BA.2, scientists analyzed a number of available sequences. This helped determine the BA.2 signature mutation. Furthermore, to evaluate the outcome of these mutations, the authors examined the structure of the spike receptor binding domain (S-RBD) of Wuhan (ancestor strain) and Omicron strains that complexed with monoclonal antibodies (mAbs). I analyzed it.

In this study, researchers identified mutations in BA.1 and BA.2 from sequences taken from the GISAID repository. These sequences were aligned using various sequence alignment programs such as MEGA X, MAFFT, and JalView to identify BA.2 signature mutations. Nextclade was used to measure amino acid changes and thereby identify BA.2 mutations. In this study, scientists considered mutations that were more than 50% prevalent as signature mutations.

Main survey results

In the current study, researchers analyzed the mutation profile of BA.2 and compared it to BA.1 (the original Omicron strain). They reported that there were significant differences in the number and distribution of mutations between the BA.2 and BA.1 omicron strains. Structural data show that BA.2 maintains significant contact with the host’s ACE2. This is the main invasion mode of the virus. In addition, this variant showed avoidance or reduced binding by neutralizing mAbs. Scientists have stated that the combination of these two factors makes BA.2 a surprising variant that can affect existing and future COVID-19 vaccination strategies.

Researchers have found that BA.2 retains the majority of BA.1 mutations, including mutations such as the delta variant G142D, which is involved in mAb avoidance or reduced binding capacity of them compared to the original strain. I reported that I got more. Current studies have revealed that BA.2 variants are evolving and contain specific mutations associated with S proteins and antibodies.

Determining the functions associated with BA.2 mutations in the ORF outside the region encoding the S protein was difficult. This is because the frequency of reported S protein structures is significantly higher than that of nsp structures. In addition, researchers structurally predict the role of mutations in proteins with multiple enzymatic functions (nsp3, nsp5, nsp12, nsp13, etc.) unless mutations occur in highly conserved active sites. Faced with difficulties.

Conclusion

The authors emphasized that one of the limitations of this study was that all sequences were taken from the GISAID repository to analyze the BA.1 and BA.2 mutations. These sequences had high coverage and quality, but some sequences contained gaps in different genes. This limited the identification of some mutations in a particular gene.

Scientists believe that new Omicron strains have emerged from unvaccinated or immune-protected individuals. In this study, the authors found that the BA.2 strain was a key mutation that not only reduced the effectiveness of the neutralized mAb, but also retained the same receptor-mediated invasion activity as the SARS-CoV-2 ancestral strain. Pointed out that is included.