Functional characterization of spike RBD mutations in SARS-CoV-2 Omicron-derived subvariants KP.3.1.1, LP.8.1, and NB.1.8.1.
Year: 2026
Type: article
Abstract: Following the global spread of SARS-CoV-2 Omicron (B.1.1.529), its subvariants KP.3.1.1, LP.8.1, and NB.1.8.1 disseminated worldwide. By April 2025, the epidemiological landscape of these subvariants had become distinct, with LP.8.1 emerging as the predominant variant, KP.3.1.1 persisting as a co-circulating variant under monitoring (VUM), and NB.1.8.1 exhibiting a significant increase in prevalence. Despite their epidemiological prominence, the functional consequences of spike mutations defining these emerging subvariants remain poorly understood. Here, we systematically dissected the entry properties conferred by their receptor-binding domain (RBD) mutations using a pseudovirus system. Our results demonstrate that all three subvariants exhibited substantially higher infectivity than ancestral Omicron. Unexpectedly, this enhanced infectivity occurred despite reduced ACE2 binding affinity. Rather, increased viral entry consistently correlated with elevated spike cleavage efficiency and fusogenicity, suggesting a compensatory evolutionary strategy in which enhanced spike processing and fusion contribute to enhanced entry despite reduced receptor engagement. These findings provide a virological explanation for the accelerated global spread of these subvariants and highlight the importance of monitoring functional shifts in spike-mediated entry that may influence SARS-CoV-2 transmission dynamics.
Source: The Journal of Microbiology
DOI: 10.71150/jm.2511014
Authors: Yeong Jun Kim, Seon Jae Jeong, Hye-Ra Lee
Institution: Korea University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,690
OpenAlex ID: W7150817224