Fig. 1: The influence of V483del on SARS-CoV-2 viral fitness.

a Diagram illustrating the full-length S protein sequence of BA.2.86. Newly added mutations were indicated in blue, while deleted site of RBD was shown in red. b Statistical analysis of sarbecoviruses capable of utilizing hACE2. Black font represents coronaviruses retaining residue 483 (WT SARS-CoV-2 sequence number), while red font represents viruses lacking residue 483 (WT SARS-CoV-2 sequence number). c Comparison of the affinity of ACE2 from different species for SARS-CoV-2 variants, with species ranked by the amino acid sequence differences from hACE2. d Determination of the affinity and infectivity of BA.2.86 and BA.2.86-V483ins to different species. Blue bars represent BA.2.86, and orange bars represent BA.2.86-V483ins. e Overall structures of BA.2.86 S-trimer in complex with bACE2 and BA.2.86-V483ins RBD in complex with bACE2. f Detailed information on the interactions of hACE2, bACE2 with BA.2.86, BA.2.86-V483ins RBD. Residues involved in the hydrophobic interactions are shown as transparent surfaces and hydrogen bonds are marked with yellow dashed lines. Note that the complex structure of hACE2 and BA.2.86-V483ins RBD was generated using molecular docking. g The infectivity of XBB.1.5, XBB.1.5-∆483 and BA.2.86, BA.2.86-V483ins was evaluated in 293T, Huh-7 cells overexpressing hACE2. The evaluation was performed using a Vesicular stomatitis virus-based pseudovirus system. Error bars represent the mean ± SD of three replicates. h Evaluation of cell fusion ability of BA.2.86 and BA.2.86-V483ins. i Evaluation of cleavage efficiency of BA.2.86 and BA.2.86-V483ins. j, k Single immunity background and mimicking real-world infection background of BALB/c mice were used to evaluate the immunogenicity of BA.2.86 and BA.2.86-V483ins. Left panel, neutralization titers against BA.2.86-derived variants after immunization with BA.2.86. Middle panel, neutralization titers against BA.2.86-derived variants after immunization with BA.2.86-V483ins. Right panel, comparison of neutralization titer of BA.2.86 and BA.2.86-V483ins after immunization with autoantigen. l The evasion potential of BA.2.86 and BA.2.86-V483ins against antibodies generated by XBB.1.5 and EG.5.1.