Evolutionary trajectories and mechanisms driving the emergence of the post-Omicron SARS-CoV-2 lineage

In a recent report posted on virology*, in a discussion forum for the analysis of viral genomes, researchers summarized the mechanisms by which new omicron substrains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolve.

Background

Over time, SARS-CoV-2 exhibited a unique evolutionary trait called saltation. This is the ability to generate variants characterized by long phylogenetic branch lengths and the absence of genetic intermediates. These new Omicron subvariants resemble older rather than modern SARS-CoV-2 strains like norovirus strains, but are distinct from other common respiratory viruses.

Survey results

The research community has hypothesized that this type of evolution is the result of the re-emergence of viruses that evolved during long-term chronic infection. Due to their sex, these variants were able to accumulate mutations rapidly. Most of the SARS-CoV-2 variants of concern (VOCs) (e.g. alpha, beta, gamma, omicron) have evolved from prevariant precursors and are ‘first generation’ salutation variants.

In the case of SARS-CoV-2, this evolutionary pattern continued until 2022, giving rise to the second generation salutation subspecies. These are all subspecies of Omicron. Examples: BA.2-Derivatives, BA.2.75, BA.2.3.20, BJ.1, BS.1, BA.2.83, BA.2.10.4, BP.1, and DD.1. Primarily, they evolved as a result of seeding events in late 2021 or early 2022.

These omicron subvariants have multiple non-synonymous mutations nested within the receptor-binding domain (RBD) and N-terminal domain (NTD) of the SARS-CoV-2 spike (S). glycoproteinBA.2.75 is by far the most prevalent, but BA.2.3.20 has also shown considerable growth over the past few months.

SARS-CoV-2, like all coronavirus, is highly susceptible to interlineage recombination. As a result, by November 2022, researchers had identified 54 of Pango’s designated SARS-CoV-2 interlineage recombinants. These are all denoted with the prefix X-. Notably, these recombinants between divergent variants usually get some favorable mutations from both parents. However, they only defeated their parental lineage when they were on a steep decline trajectory while the next subspecies was still evolving.

So far, XBB, which is likely a recombination between BJ.1 and the BA.2.75 derivative BM.1.1.1, is the most prominent interstrain recombinant. He inherits the 5′ and 3′ parts of the genome from the former and the latter, respectively, and has only one breakpoint within the S RBD. Its single S breakpoint enabled XBB to harbor the most potent antigenic RBD mutations, making it relatively (antigenically) distant from previous variants. XBD and XBF are two other prominent modern recombination strains that are recombination between Omicron BA.5 and BA.2.75 substrains.

Complex recombinants such as XAY, XBA, XWA, and XBC came into existence due to recombination events between non-cocirculating lineages such as Delta and BA.2. Unlike simple recombinants, they contain 3-8 breakpoints and more undisclosed mutations. They did not acquire these mutations from either parental strain. Surprisingly, XAY and XBA are complex recombinants, sharing parts of the genome and even private mutations, suggesting that they likely arose from the same parental lineage. increase.

The researchers concluded that the ‘complex’ recombinant likely also arose from chronic infection of individuals infected with coronavirus disease 2019 (COVID-19) first from Delta and then reinfected from BA.2. I think. Currently, XBC and XAY appear to be the most prevalent, although both of these strains have fewer antigenic RBD mutations than the cocirculating and rapidly growing BQ.1.1 or XBB strains. increase. Therefore, it is unlikely to persist in the long term.

Effects of antigenic drift and convergent mutations in SARS-CoV-2

BA.5 is a potent antigenic mutation in contrast to BA.2, the predecessor Omicron-derived salt addition variant that acquired these mutations at once to replace the latter globally in mid-2022. was accumulated continuously. Another rapidly growing lineage is her BQ.1.1, a derivative of BQ.1, which contains three additional antigenic variants in her S RBD. Other examples include BA.2.75.2, which had a few more antigenic RBD mutations than its parental BA.2.75. Overall, this drift-like evolutionary pattern resembles the continuous antigenic drift of seasonal influenza viruses.

Saltation, drift, and recombinant SARS-CoV-2 variants have also undergone an unusual convergent evolution, especially at antigenic RBD sites. They showed substitutions such as R346X, K444X, and reversions such as F490X and R493Q. Moreover, they had several deletions in the ~144 NTD region and appeared in multiple phylogenetic branches. However, it is unclear whether such mutations continuously accumulate at non-dominant sites over time or slow down to adversely affect viral fitness.

Conclusion

BQ.1.1, XBB, and CH.1.1 are now likely to be the fastest growing SARS-CoV-2 variants in the world, and in the coming months, together or individually, new COVID-19 Can cause -19 waves. However, all of these could co-circulate, albeit temporarily, unless a more suitable SARS-CoV-2 variant emerges. Despite sharing viral, epidemiological, and clinical characteristics with their parental lineages, these lineages are all genetically and antigenically distant from previous Omicron lineages.

Another ‘omicron-like event’ might simply generate new variants with orthogonal antigenicity from these circulatory lineages. should be prepared. But the most threatening is the emergence of saltation variants from Delta VOC. Delta sequences continue to be sampled worldwide by genome sequencing methods, and since most carry multiple individual mutations, the threat of potentially sizeable delta reservoirs is real.

In conclusion, the researchers emphasized the continuing need for genomic surveillance and analysis of SARS-CoV-2 on a global and equitable basis. Currently missing or inconsistent. Policy makers may halt other pandemic measures, but SARS-CoV-2 continues to evolve using unpredictable mechanisms. Such surveillance measures will ensure a rapid response to emerging SARS-CoV-2 variants.

*Important Notices

Virological is a discussion forum for the analysis and interpretation of viral molecular evolution and epidemiology. The report has not been peer-reviewed and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information.