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Special Issues
- Pioneering strategies for overcoming bacterial drug resistance (2026)
- Advancing microbial engineering through synthetic biology (2025)
- Host-associated microbiome (2024)
- Bacterial regulatory mechanisms for the control of complex cellular mechanisms (2023)
- Two years into COVID-19 pandemic: Where are we? (2022)
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Article
- 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.
- Yeong Jun Kim, Seon Jae Jeong, Hye-Ra Lee
- Received November 17, 2025 Accepted January 14, 2026 Published online April 6, 2026
- DOI: https://doi.org/10.71150/jm.2511014 [Epub ahead of print]
- 57 View
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Abstract
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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.
Review
- The rapid adaptation of SARS-CoV-2–rise of the variants: transmission and resistance
- Sandrine M. Soh , Yeongjun Kim , Chanwoo Kim , Ui Soon Jang , Hye-Ra Lee
- J. Microbiol. 2021;59(9):807-818. Published online August 27, 2021
- DOI: https://doi.org/10.1007/s12275-021-1348-5
- 576 View
- 3 Download
- 17 Web of Science
- 16 Crossref
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Abstract
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- The causative factor of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously mutating. Interestingly, identified mutations mainly occur in the spike (S) protein which interacts with the ACE2 receptor and is cleaved via serine protease TMPRSS2. Some mutated strains are becoming dominant in various parts of the globe because of increased transmissibility as well as cell entry efficacy. Remarkably, the neutralizing activity of monoclonal antibodies, convalescent sera, and vaccines against the variants has been reported to be significantly reduced. Therefore, the efficacy of various monoclonal antibodies therapy and vaccines against these variants is becoming a great global concern. We herein summarize the current status of SARS-CoV- 2 with gears shifted towards the recent and most common genetic variants in relation to transmission, neutralizing activity, and vaccine efficacy.
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Citations
Citations to this article as recorded by
- Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine
Yasunari Matsuzaka, Ryu Yashiro
BioMedInformatics.2024; 4(2): 1531. CrossRef - Complex vaccination strategies prevent the emergence of vaccine resistance
Simon A Rella, Yuliya A Kulikova, Aygul R Minnegalieva, Fyodor A Kondrashov, Ben Ashby, Tim Connallon
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Journal of Microbiology and Biotechnology.2023; 33(12): 1587. CrossRef - Analysis of 3.5 million SARS-CoV-2 sequences reveals unique mutational trends with consistent nucleotide and codon frequencies
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Ananya Chugh, Nimisha Khurana, Kangna Verma, Ishita Sehgal, Rajan Rolta, Pranjal Vats, Rajendra Phartyal, Deeksha Salaria, Neha Kaushik, Eun Ha Choi, Mansi Verma, Nagendra Kumar Kaushik
Applied Sciences.2022; 12(11): 5546. CrossRef - The SARS-CoV-2 differential genomic adaptation in response to varying UVindex reveals potential genomic resources for better COVID-19 diagnosis and prevention
Naveed Iqbal, Muhammad Rafiq, Masooma, Sanaullah Tareen, Maqsood Ahmad, Faheem Nawaz, Sumair Khan, Rida Riaz, Ting Yang, Ambrin Fatima, Muhsin Jamal, Shahid Mansoor, Xin Liu, Nazeer Ahmed
Frontiers in Microbiology.2022;[Epub] CrossRef - SARS-CoV-2 Variants of Concern Hijack IFITM2 for Efficient Replication in Human Lung Cells
Rayhane Nchioua, Annika Schundner, Dorota Kmiec, Caterina Prelli Bozzo, Fabian Zech, Lennart Koepke, Alexander Graf, Stefan Krebs, Helmut Blum, Manfred Frick, Konstantin M. J. Sparrer, Frank Kirchhoff, Tom Gallagher
Journal of Virology.2022;[Epub] CrossRef - Viral Load in COVID-19 Patients: Implications for Prognosis and Vaccine Efficacy in the Context of Emerging SARS-CoV-2 Variants
Severino Jefferson Ribeiro da Silva, Suelen Cristina de Lima, Ronaldo Celerino da Silva, Alain Kohl, Lindomar Pena
Frontiers in Medicine.2022;[Epub] CrossRef - Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants
Lili Li, Meiling Gao, Peng Jiao, Shulong Zu, Yong-qiang Deng, Dingyi Wan, Yang Cao, Jing Duan, Saba R Aliyari, Jie Li, Yueyue Shi, Zihe Rao, Cheng-feng Qin, Yu Guo, Genhong Cheng, Heng Yang
Cell & Bioscience.2022;[Epub] CrossRef - Perspectives and Factors Affecting the Preventive Behavior Pertinent to COVID-19 among School Employees in Chiang Mai, Thailand: A Cross-Sectional Study
Pheerasak Assavanopakun, Tharntip Promkutkao, Suchat Promkutkeo, Wachiranun Sirikul
International Journal of Environmental Research and Public Health.2022; 19(9): 5662. CrossRef - Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2): results of a randomised, double-blind, placebo-controlled, phase 3 trial
Karin Hardt, An Vandebosch, Jerald Sadoff, Mathieu Le Gars, Carla Truyers, David Lowson, Ilse Van Dromme, Johan Vingerhoets, Tobias Kamphuis, Gert Scheper, Javier Ruiz-Guiñazú, Saul N Faust, Christoph D Spinner, Hanneke Schuitemaker, Johan Van Hoof, Macay
The Lancet Infectious Diseases.2022; 22(12): 1703. CrossRef - Fundamentals of genomic epidemiology, lessons learned from the coronavirus disease 2019 (COVID-19) pandemic, and new directions
Denis Jacob Machado, Richard Allen White, Janice Kofsky, Daniel A. Janies
Antimicrobial Stewardship & Healthcare Epidemiology.2021;[Epub] CrossRef - Daily Physical Activity and Sleep Measured by Wearable Activity Trackers during the Coronavirus Disease 2019 Pandemic: A Lesson for Preventing Physical Inactivity during Future Pandemics
Hidetaka Hamasaki
Applied Sciences.2021; 11(21): 9956. CrossRef - The adaptation of SARS-CoV-2 to humans
Eduardo Tosta
Memórias do Instituto Oswaldo Cruz.2021;[Epub] CrossRef
- Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine
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