SARS-CoV-2 XEC: A Genome-Based Survey

Abstract

Recombination, a process of genetic exchange between distinct organisms, has played a critical role in the emergence of SARS-CoV-2 variants such as the XEC recombinant. This study provides a detailed genomic and structural characterization of XEC, derived from the recombination of lineages KP.3.3 (donor) and KS.1.1 (acceptor). Phylogenomic analyses reveal that XEC and its descendant XEC.1 form a monophyletic clade with close evolutionary ties to KP.3.3. The genomic breakpoint, spanning nucleotide positions 22,363-22,463, marks the shift from KS.1.1 to KP.3.3 within the spike protein gene. Mutational analysis highlights shared traits with its parental lineages, including mutations associated with immune evasion, receptor affinity, and fusogenicity. Notable changes, such as Q493E and L455S, may confer unique immunogenic properties, though XEC's overall immune escape potential is limited by the absence of new mutations in conserved epitopes. Despite these mutations, XEC demonstrates restricted geographical spread, low genetic variability, and an evolutionary trajectory indicative of an evolutionary dead-end. Bayesian Skyline Plot analysis corroborates this, showing stable but declining population size. These findings underscore the need for ongoing genomic surveillance to monitor recombinant variants' characteristics and public health impact. This study contributes to understanding viral evolution and highlights the importance of distinguishing variants of concern from those with minimal epidemiological significance.

Keywords: SARS-CoV-2; XEC recombinant; evolutionary trajectory; genetic diversity; genomic surveillance; pandemic monitoring; phylogenomic analysis; spike protein mutations; viral recombination.

Figure 1

The time-scaled phylogenetic tree highlights strains within a global representative subsample of 491 out of 4063 SARS-CoV-2 genomes collected between April and December 2024. The phylogenetic analysis was performed using the nextstrain/ncov tool (https://github.com/nextstrain/ncov, accessed on 4 December 2024) and is available at https://gisaid.org/phylodynamics/global/nextstrain/ (accessed on 4 December 2024). The figure was refined using GIMP 2.8 software (available at https://www.gimp.org/downloads/oldstable/, accessed on 6 December 2024).

Figure 2

Bayesian Skyline Plot—BSP (A)—and Lineages Through Time—LLT (B)—of the recombinant lineage SARS-CoV-2 XEC. The viral effective population size (A) and the number of lineages (B) in the y-axis are plotted on the y-axis against the corresponding dates on the x-axis. The figure was refined using GIMP 2.8 software (available at https://www.gimp.org/downloads/oldstable/, accessed on 6 December 2024).

Figure 3

Comparison of the interfaces between ACE2 (orange) and the RBD of the JN.1 (A), KP.3.3 and XEC (B), and KS.1.1 (C) variants. Protein backbone is displayed as cartoon models while relevant side chains are depicted as labeled stick models.