SARS-CoV-2 BA.2.86 is susceptible to the neutralizing antibody MO11 targeting subdomain 1 despite the E554K mutation near the epitope

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FIG 1 The SD1-targeting antibody MO11 still retains the neutralizing activity against SARS-CoV-2 BA.2.86.(A) The location of SD1 in spike (top) and the three mutations emerged in BA.2.86 (bottom) are shown.The residues in the footprint of the MO11 revealed by cryoEM analysis (1) are painted in orange.The N-glycosylation site at residue N331, which is also involved in the MO11 footprint, is indicated as a branch mark.(B) The binding mode (left) and footprint of MO11 on the SARS-CoV-2 spike SD1 (right, PDB: 8XI6) (1).The residues within 4 Å from MO11 are painted.The three mutation sites in the SD1, that is I332, A570, and E554, are painted in gray.(C) Reactivity of MO11 to BQ.1.1 spike ectodomain with or without E554K mutation.ELISA was performed as described previously (1).(D) Reactivity of MO11 to the EG.5.1 or BA.2.86 spike ectodomains.(E) Neutralizing activity of MO11 against SARS-CoV-2 spike pseudotyped VSV-ΔG (2, 3).The viruses were pseudotyped with spikes of BQ.1.1,BQ.1.1 with the E554K mutation (BQ.1.1E554K), or BA.2.86 and mixed with indicated antibodies at a final concentration of 5 µg/mL at 37°C for 1 hour before infecting the VeroE6/TMPRSS2 cells.The luminescence signal was measured 1 day post-infection, and the values were normalized as the fold change relative to the values of no antibody (no Ab) condition.Means of the three independent experiments are shown with the standard deviations.The P values of Student's t-test for the difference between the MO11 and the negative control (MO1) are shown above respective data.

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