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

Zhang L, Kempf A, Nehlmeier I, Chen N, Graichen L, Moldenhauer AS, Stankov MV, Happle C, Schulz S, Dopfer-Jablonka A, Jäck HM, Behrens GM, Pöhlmann S, Hoffmann M (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Virology Elsevier

Book Volume: 612

Article Number: 110675

DOI: 10.1016/j.virol.2025.110675

Abstract

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.

Authors with CRIS profile

Sebastian Schulz Professur für Translationale Immunologie Hans-Martin Jäck Department of Molecular Immunology

Involved external institutions

Deutsches Primatenzentrum (DPZ), Leibniz-Institut für Primatenforschung DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Deutsches Zentrum für Infektionsforschung (DZIF) DE Germany (DE)

How to cite

APA:

Zhang, L., Kempf, A., Nehlmeier, I., Chen, N., Graichen, L., Moldenhauer, A.S.,... Hoffmann, M. (2025). Host cell entry efficiency and neutralization sensitivity of the SARS-CoV-2 MC.10.1 variant. Virology, 612. https://doi.org/10.1016/j.virol.2025.110675

MLA:

Zhang, Lu, et al. "Host cell entry efficiency and neutralization sensitivity of the SARS-CoV-2 MC.10.1 variant." Virology 612 (2025).

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