Host cell entry efficiency and neutralization sensitivity of the SARS-CoV-2 MC.10.1 variant

New SARS-CoV-2 variants continue to emerge and may cause new waves of COVID-19. Antibody evasion is a major driver of variant emergence but variants can also exhibit altered capacity to enter lung cells and to use ACE2 species orthologues for cell entry. Here, we assessed cell line tropism, usage of ACE2 orthologues and antibody evasion of variant MC.10.1. This variant arose from the highly prevalent KP.3.1.1 variant, reached a prevalence of 10–15 % in certain countries in the spring of 2025 and contains a single amino acid mutation in the spike (S) protein, A435S, relative to the KP.3.1.1 S protein. We found that MC.10.1 and the parental KP.3.1.1 S protein show similar expression and similar capacity to fuse cells and to use ACE2 orthologues from different species for entry. In contrast, MC.10.1 S protein-driven entry into Calu-3 lung cells was reduced as compared to the KP.3.1.1 S protein. Finally, MC.10.1 S protein-bearing particles were less susceptible to neutralization by antibodies induced upon vaccination with the JN.1 booster vaccine as compared to their counterparts bearing KP.3.1.1 S protein. Collectively, our results indicate increased antibody evasion but reduced cell entry efficiency of variant MC.10.1.