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Functional characterization of spike RBD mutations in SARS-CoV-2 Omicron-derived subvariants KP.3.1.1, LP.8.1, and
Yeong Jun Kim1, Seon Jae Jeong1, Hye-Ra Lee1,2
1Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong 30019, Republic of Korea.
Journal of Microbiology (Seoul, Korea)
|April 6, 2026
Summary
New SARS-CoV-2 Omicron subvariants show increased infectivity due to enhanced spike processing and fusion, not ACE2 binding. This explains their rapid global spread and highlights the need for monitoring viral entry dynamics.
Area of Science:
- Virology
- Molecular Biology
- Epidemiology
Background:
- The global spread of SARS-CoV-2 Omicron (B.1.1.529) led to the emergence of subvariants KP.3.1.1, LP.8.1, and NB.1.8.1.
- By April 2025, LP.8.1 became predominant, KP.3.1.1 remained a variant under monitoring (VUM), and NB.1.8.1 showed increased prevalence.
- The functional impact of spike mutations in these subvariants on viral entry remains unclear.
Purpose of the Study:
- To investigate the entry properties conferred by receptor-binding domain (RBD) mutations in SARS-CoV-2 Omicron subvariants KP.3.1.1, LP.8.1, and NB.1.8.1.
- To understand the virological mechanisms underlying the increased transmission of these subvariants.
- To assess the impact of RBD mutations on viral infectivity, ACE2 binding, spike cleavage, and fusogenicity.
Main Methods:
- Utilized a pseudovirus system to systematically analyze the entry properties of SARS-CoV-2 subvariants.
- Quantified infectivity, ACE2 binding affinity, spike cleavage efficiency, and viral fusogenicity for each subvariant.
- Compared functional properties against ancestral Omicron.
Main Results:
- All three subvariants (KP.3.1.1, LP.8.1, NB.1.8.1) demonstrated significantly higher infectivity than ancestral Omicron.
- Enhanced infectivity was observed despite reduced ACE2 binding affinity in these subvariants.
- Increased viral entry correlated with enhanced spike cleavage efficiency and fusogenicity, suggesting a compensatory mechanism.
Conclusions:
- The enhanced infectivity of SARS-CoV-2 Omicron subvariants is attributed to improved spike processing and fusion, rather than increased ACE2 binding.
- These findings provide a virological basis for the accelerated global dissemination of these subvariants.
- Monitoring functional shifts in spike-mediated viral entry is crucial for understanding SARS-CoV-2 transmission dynamics.
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