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

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Emerging SARS-CoV-2 variants pose ongoing risks for COVID-19 waves.
• Antibody evasion is a key factor in variant emergence, alongside altered cell entry mechanisms.

Purpose of the Study:

• To evaluate the cell tropism, ACE2 orthologue usage, and antibody evasion properties of the SARS-CoV-2 variant MC.10.1.
• To compare MC.10.1 with its parental variant KP.3.1.1.

Main Methods:

• Assessed cell line tropism and ACE2 orthologue usage for MC.10.1 and KP.3.1.1 spike proteins.
• Evaluated antibody neutralization of MC.10.1 using antibodies from JN.1 booster vaccination.

Main Results:

• MC.10.1 and KP.3.1.1 spike proteins exhibited similar expression, cell fusion capacity, and ACE2 orthologue usage.
• MC.10.1 demonstrated reduced entry into Calu-3 lung cells compared to KP.3.1.1.
• Particles bearing MC.10.1 spike protein showed decreased susceptibility to neutralization by JN.1 booster-induced antibodies.

Conclusions:

• Variant MC.10.1 exhibits enhanced antibody evasion capabilities.
• MC.10.1 displays reduced cell entry efficiency into lung cells compared to its predecessor.
• These findings highlight the evolving nature of SARS-CoV-2 and potential implications for vaccine effectiveness.