Guo, C.; Yu, Y.; Liu, J.; Jian, F.; Yang, S.; Song, W.; Shao, F.; Yu, L.; Cao, Y.

The emergence of the SARS-CoV-2 saltation variant BA.3.2, which harbors over 50 mutations relative to its ancestral BA.3 lineage, has raised concerns about its potential to drive outbreaks similar to BA.2.86/JN.1. Concurrently, variants such as NB.1.8.1, LF.7.9, XEC.25.1, XFH, and XFG exhibit enhanced growth advantages over LP.8.1.1, necessitating a comparative analysis of their antigenic and virological characteristics. Here, we evaluated the infectivity, ACE2-binding efficiency, and immune evasion of these variants. Pseudovirus assays revealed BA.3.2\'s robust antibody evasion, including resistance to Class 1/4 monoclonal antibodies; however, its ACE2 engagement efficiency was markedly reduced due to a closed spike conformation, leading to low infectivity. While XFG and LF.7.9 demonstrated strong immune escape associated with A475V and N487D mutations, their reduced receptor-binding efficiency suggested a need for compensatory adaptations. In contrast, NB.1.8.1 retained high ACE2 affinity and humoral immune evasion, supporting its potential for future dominance. Collectively, BA.3.2\'s current profile limits its ability to compete with emerging variants like NB.1.8.1. Sustained monitoring of BA.3.2\'s evolution, particularly for mutations stabilizing an open RBD conformation or enhancing escape from Class 1 antibodies, is essential to assess its outbreak potential.