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

Abstract

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that 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. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, nowadays XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.

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

“…The phylogenomic reconstruction, available at https://gisaid.org/phylodynamics/global/nextstrain/, depicts an evolutionary pattern of XBB.1.5 very similar to that of previous, recent variants such as BA.2.75, 2 BA.2.12.1 and BQ.1 10 that appeared as an evolutionary blind background. Notably, this pattern has also been identified for the original recombinant XBB and its first descendant XBB.1, 3 which are now known not to exhibit characteristics of epidemiologically dangerous lineages. Actually, the XBB.1.5 lineage represents the first descendant of the recombinant XBB for which threats on public health impact originally arose.…”

“…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.…”

“…The lineage XBB.1.5 presents the same point mutations of interest in the spike protein sequence as its progenitor XBB (i.e. K417N, S477N, N501Y and P681H) 3 , except for mutation at position 486. 8 Indeed, the NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the original Wuhan Phe (conserved in BA.2) is replaced by a Ser in XBB and XBB.1, 3 and a Pro in XBB.1.5.…”

“…K417N, S477N, N501Y and P681H) 3 , except for mutation at position 486. 8 Indeed, the NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the original Wuhan Phe (conserved in BA.2) is replaced by a Ser in XBB and XBB.1, 3 and a Pro in XBB.1.5. The predicted net electrostatic charges of the RBD and NTD domains, the changes of which have been reported to impact on virus transmissibility and infectivity, are reported in Table 1 .…”

Pathways to altered virulence of SARS-CoV-2

“…Viral recombination (as a result of coinfection) represents another pathway to large changes in viral sequence and functionality (190). Recombination events have already been documented for SARS-CoV-2-for example, the currently dominant Omicron variant sublineage, XBB, arose from a recombination event between BA.2 lineage members BJ.1 and BM.1.1.1 (192). Recombination within SARS-CoV-2 variant lineages or with other coronaviruses could offer a path to dramatic increases or decreases in SARS-CoV-2 virulence.…”