Genetic and Structural Data on the SARS-CoV-2 Omicron BQ.1 Variant Reveal Its Low Potential for Epidemiological Expansion

Abstract

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10−4 and 7 × 10−4 subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages.

Genome‐based comparison between the recombinant SARS‐CoV‐2 XBB and its parental lineages

“…Similarly to what was recently observed for the variants BA.2.75 (nicknamed Centaurus ) 27 and BQ.1 (nicknamed Cerberus ), 28 the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant that present features of concern.…”

“…In the near past the same condition was also observed in the BA.2.12.1 variant which indeed has not produced further new sub‐lineages and whose genomic global sequence prevalence has been declining during time until its almost complete disappearance. Indeed, in the phylogenomic reconstruction, BA.2.12.1 variant (GISAID Clade 22C), BA.2.75 (GISAID Clade 22D), BQ.1 (GISAID Clade 22E) presented branches’ length that suggested the lack of a rapid diversification, 27,28 similarly to the clade composed of XBB + XBB.1 in the current reconstruction, which does not highlight any features typical of an epidemiologically dangerous lineage at the beginning of its evolutionary path.…”

“…As recently pointed out for several variants newly generated (i.a. BA.2.75 and BQ.1) this is not the feature of a highly expansive variant,27,28 which typically explodes much faster in terms of numbers of infections and population size, as it occurred for the Omicron variant (B.1.1.529) for instance, which became predominant in a few time 29. Indeed, BSP indicates an initial period of about 60 days with a flattened genetic variability and a very small viral population size.…”

Genetic and structural genome-based survey reveals the low potential for epidemiological expansion of the SARS-CoV-2 XBB.1.5 sublineage

“…However, the Bayesian Skyline Plot (BSP) in Fig. 1 (estimated on all high quality genomes and coverage available on January 13, 2023 form the GSAID portal (https://gisaid.org/) by following Scarpa et al 2 , 3 , 5 ), indicates quite a low level of genetic variability with very few fluctuation points over time. The viral genetic variability and the population size peaked reaching the plateau around November 24, 2022.…”

Is a new COVID‐19 wave coming from China due to an unknown variant of concern? Keep calm and look at the data

“…Thus, there is a need to gain fundamental knowledge about the epidemiological characteristics of a new variant or infection, from transmission potential to natural history. [5][6][7][8] We spent the first days of 2023 in the "shadow of the dragon," with the fear of a China as the engine of a new wave of COVID-19, linked, perhaps, to unknown and mysterious variants that are more contagious and aggressive. A shadow that brings to mind what was already experienced 3 years ago, at the beginning of the pandemic.…”