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

Area of Science:

• Virology
• Genomics
• Evolutionary Biology

Background:

• Recombination drives RNA virus evolution, with SARS-CoV-2 generating multiple recombinants during the pandemic.
• The XBB lineage (Gryphon) is a recent SARS-CoV-2 recombinant derived from BJ.1 and BM.1.1.1.

Purpose of the Study:

• To compare the SARS-CoV-2 XBB recombinant with its parental lineages using genome-based analysis.
• To assess the evolutionary trajectory and potential of the XBB lineage and its descendant XBB.1.

Main Methods:

• Genome-based survey and comparative genetic analysis of SARS-CoV-2 lineages.
• Bayesian Skyline Plot analysis to infer population dynamics and genetic variability.
• Structural analysis of the Receptor Binding Domain (RBD) for ACE2 affinity.

Main Results:

• XBB and XBB.1 exhibit characteristics of an evolutionary "blind alley" with limited potential for further epidemiologically significant descendants.
• While genetic variability and expansion capabilities are slightly higher than parental lineages, XBB reached a population plateau and subsequent decrease in variability.
• XBB.1 showed increased genetic variability and reached its own plateau, exhibiting vicariance with its progenitors; XBB/XBB.1 RBDs have weaker ACE2 affinity compared to BA.2 RBD.

Conclusions:

• Currently, XBB and XBB.1 do not indicate significant danger or high expansion capability.
• Ongoing genome-based monitoring is crucial to identify potential future mutations that could increase the pathogenicity or expansion capacity of SARS-CoV-2 variants.