Continued Complexity of Mutations in Omicron Sublineages

Abstract

The latest SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529), has diversified into more than 300 sublineages. With an expanding number of newly emerging sublineages, the mutation profile is also becoming complicated. There exist mutually exclusive and revertant mutations in different sublineages. Omicron sublineages share some common mutations with previous VOCs (Alpha, Beta, Gamma, and Delta), indicating an evolutionary relationship between these VOCs. A diverse mutation profile at the spike–antibody interface, flexibility of the regions harboring mutations, mutation types, and coexisting mutations suggest that SARS-CoV-2’s evolution is far from over.

Effects of Epitranscriptomic RNA Modifications on the Catalytic Activity of the SARS‐CoV‐2 Replication Complex**

“…The RNA extension results with 1 f as the template indicated that m 1 A has a dramatic effect on the activity of SC2RC. The reaction was largely stopped with only a tiny portion of the primer being able to be extended beyond the modified nucleotide.…”

“…[19] With a possibility of installation of m 1 A to the SARS-CoV-2 genome, one would predict that individuals with clinical conditions having increased ability for m 1 A installation would be less likely to be infected by the virus. However, it is well documented that people with cancer, obesity and diabetes are more vulnerable to COVID-19, [20] and these individuals have been reported to have elevated m 1 A modification and the modification has negative effects on prognosis of their clinical conditions. [21] Therefore, their transcriptomic machinery would be more likely to install m 1 A onto the SARS-CoV-2 genome and they would do better for COVID-19 than the general population without considering other factors such as induced immunity.…”

“…The coronavirus disease 2019 (COVID‐19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has inflicted enormous loss of human lives and devastating economic hardship across the globe. Although several vaccines and medications have been developed and the situation has improved, the seemingly endless mutation of the genome of SARS‐CoV‐2 and the emergence of new strains of the virus continue to cause grave concerns [1] . In the face of the challenges, one of the questions people often ask is why the virus causes different symptoms and different degrees of harmfulness to different individuals [2] .…”

“…Although several vaccines and medications have been developed and the situation has improved, the seemingly endless mutation of the genome of SARS-CoV-2 and the emergence of new strains of the virus continue to cause grave concerns. [1] In the face of the challenges, one of the questions people often ask is why the virus causes different symptoms and different degrees of harmfulness to different individuals. [2] For example, why do individuals with preexisting conditions such as cancer, diabetes and obesity have more severe symptoms?…”

Underlying driving forces of the SARS-CoV-2 evolution: immune evasion and ACE2 binding affinity

“…Recently, a large number of immune-evasive BA.2 and BA.4/5 subvariants were emerging in the population 15,16 , implying the evolution of SARS-CoV-2 might be accelerating. To verify this hypothesis, we retrieved 200 sequences per month between January 2020 and November 2022 to estimate the mutation rate of SARS-CoV-2 over time, the automatic piecewise linear regression analysis found two turning points associated with a dramatic rise in the mutation number (Figure 1A), corresponding to the emergence of the Alpha and the Omicron variants, which had a sheer number of mutations relative to their possible predecessors.…”