OmniVira

Immune evasion, infectivity, and membrane fusion of SARS-CoV-2 variants LP.8.1.1, XEC.25.1, XFG, and NB.1.8.1.

Feng Jiang1,2,3,4 Miao Zheng5 Long Gao6 Yanhang Zhuo1,2,3 Xiaoqin Liang1,2,3,4 Zhiwei Chen7,8 Xinghua Huang1,2,3 Yisheng Chen1,2,3 Zhaonan Zeng1,2,3 Yufan Xiao1,3,9 Xiaohong Du10,11 Frank Xiao-Feng Qin10 Weihua Liu12 Haijun Tang1,2,3,10
Affiliations 12 institutions
  1. Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.
  2. Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, Fujian, China.
  3. Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
  4. Department of Pain Management and Vascular Surgery & Interventional Oncology, Fujian Provincial Hospital, Fuzhou, Fujian, China.
  5. College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
  6. Department of Infectious Disease, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  7. Fuzhou Center for Disease Control and Prevention, Fuzhou, Fujian, China.
  8. Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
  9. Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, Fujian, China.
  10. National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China.
  11. Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China.
  12. Department of Nephrology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
PMID42400485 DOI10.1128/spectrum.03826-25 Year2026 Journal Microbiology spectrum Microbiol Spectr Languageeng Statusaheadofprint

Abstract

Emerging SARS-CoV-2 variants, with potentially enhanced immune evasion and transmissibility, pose a serious challenge to public health. This study provides a systematic characterization of the virological features of JN.1 descendant subvariants, including LP.8.1.1, KP.3, XEC.25.1, XFG, and NB.1.8.1, focusing on their infectivity, receptor binding, membrane fusion, and immune evasion capacity. Multiple JN.1 descendant variants exhibited reduced infectivity across various human cell lines, whereas XEC.25.1 and NB.1.8.1 demonstrated significantly enhanced cellular infectivity. JN.1 descendant variants retained the capability to infect cells expressing ACE2 orthologs from diverse mammalian species, indicating their persistent risk of zoonotic transmission. Notably, NB.1.8.1 exhibited the highest ACE2-binding affinity among all tested variants, while XEC.25.1 shows superior membrane fusion activity, particularly in cells expressing TMPRSS2. Serum neutralization assays revealed that LP.8.1.1, KP.3, XEC.25.1, XFG, and NB.1.8.1 exhibited enhanced immune evasion capabilities compared to the JN.1 strain, which was closely associated with their rapid transmission. These findings reveal that emerging JN.1 subvariants accelerate viral transmission by altering receptor-binding affinity, optimizing cellular entry efficiency, and enhancing immune evasion. Therefore, it is necessary to update vaccines and improve antiviral treatment strategies to meet the public health challenges posed by these variants. SARS-CoV-2 JN.1 has continuously evolved during the epidemic, giving rise to multiple descendant variants. Currently, JN.1 sublineages NB.1.8.1, XFG, XEC.25.1, and LP.8.1.1 have emerged as the predominant circulating variants globally. The cellular infectivity, cross-species transmission potential, and immune evasion capacity of these emerging variants remain poorly characterized. This study employed a VSV pseudovirus system to characterize the virological features of JN.1 descendant subvariants. We found that the cellular infectivity of JN.1 descendant variants was significantly altered, which may be attributed to changes in receptor-binding affinity or membrane fusion activity. The emerging JN.1 subvariants retained the ability to infect cells expressing ACE2 orthologs from diverse species. Furthermore, the emerging variants LP.8.1.1, KP.3, XEC.25.1, XFG, and NB.1.8.1 exhibited enhanced immune evasion capabilities compared to the JN.1 strain. Our study underscores the importance of surveillance and virological research for emerging JN.1 descendant variants.

Supporting text Virus Host Location
immune escape 5 infectivity 7 JN.1 subvariants 1 membrane fusion 15

Evidence records

5 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Serological Evidence
1 records
OVE11766 Serological Evidence
Key finding

Serum neutralization assays showed that LP.8.1.1, KP.3, XEC.25.1, XFG, and NB.1.8.1 had enhanced immune evasion compared with the JN.1 strain.

Virus
LP.8.1.1 KP.3 XEC.25.1 XFG NB.1.8.1 Severe acute respiratory syndrome coronavirus 2
Host
Serum Context pending
Location
Not specified
Supporting text

Serum neutralization assays revealed that LP.8.1.1, KP.3, XEC.25.1, XFG, and NB.1.8.1 exhibited enhanced immune evasion capabilities compared to the JN.1 strain

Method
serum neutralization assay
Sample type
serum
Experimental Infection
3 records · 1 evidence types
Evidence type Host Range Experiment
3 records
OVE11762 Host Range Experiment
Key finding

JN.1 descendant SARS-CoV-2 variants infected cells expressing ACE2 orthologs from diverse mammalian species in a VSV pseudovirus system.

Virus
JN.1 descendant variants Severe acute respiratory syndrome coronavirus 2
Host
cells expressing ACE2 orthologs from diverse mammalian species Experimental system
Location
Not specified
Supporting text

JN.1 descendant variants retained the capability to infect cells expressing ACE2 orthologs from diverse mammalian species, indicating their persistent risk of zoonotic transmission. This study employed a VSV pseudovirus system to characterize the virological features of JN.1 descendant subvariants.

Method
VSV pseudovirus entry/infectivity assay | heterologous ACE2 ortholog expression
Experimental system
VSV pseudovirus system using ACE2-ortholog-expressing cells
OVE11763 Host Range Experiment
Key finding

Among JN.1 descendant variants, XEC.25.1 and NB.1.8.1 showed significantly enhanced infectivity in human cell lines compared to other subvariants.

Virus
XEC.25.1 NB.1.8.1 JN.1 descendant variants
Host
human cell lines Homo sapiens Experimental system
Location
Not specified
Supporting text

Multiple JN.1 descendant variants exhibited reduced infectivity across various human cell lines, whereas XEC.25.1 and NB.1.8.1 demonstrated significantly enhanced cellular infectivity.

Method
VSV pseudovirus infectivity assay
Experimental system
VSV pseudovirus system in human cell lines
OVE11764 Host Range Experiment
Key finding

The JN.1 descendant variant XEC.25.1 exhibited superior membrane fusion activity, especially in TMPRSS2-expressing cells.

Virus
XEC.25.1
Host
cells expressing TMPRSS2 Experimental system
Location
Not specified
Supporting text

XEC.25.1 shows superior membrane fusion activity, particularly in cells expressing TMPRSS2.

Method
cell–cell fusion assay | TMPRSS2 overexpression
Experimental system
cell-based membrane fusion assay with TMPRSS2 expression
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE11765 Receptor Usage
Key finding

SARS-CoV-2 subvariant NB.1.8.1 shows the highest ACE2-binding affinity among the tested JN.1 descendant variants.

Virus
NB.1.8.1
Host
Not specified
Location
Not specified
Supporting text

Notably, NB.1.8.1 exhibited the highest ACE2-binding affinity among all tested variants.

Method
receptor-binding affinity assay
Receptors
ACE2