Decoding Omicron: Genetic Insight into Its Transmission Dynamics, Severity Spectrum and Ever-Evolving Strategies of Immune Escape in comparison with other SARS-CoV-2 variants.

Diagnostic Microbiology and Infectious Disease, Journal Year: 2025, Volume and Issue: 111(3), P. 116705 - 116705

Published: Jan. 23, 2025

Language: Английский

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The JN.1 variant of COVID-19: immune evasion, transmissibility, and implications for global health

Therapeutic Advances in Infectious Disease, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 1, 2025

The emergence of the COVID-19 JN.1 variant has raised global health concerns as it gains prevalence in several regions worldwide. First identified August 2023, evolved from Omicron lineage's BA.2.86 subvariant. Patients infected with commonly exhibit symptoms such sore throat, fever, dry cough, nausea, and vomiting. While World Health Organization labeled a Variant Interest, currently presents low risk. However, its increased transmissibility, particularly cold, climates, is concerning. This review provides comprehensive overview JN.1's biological characteristics, epidemiology, immune evasion, efficacy existing antiviral treatments vaccination strategies. A literature search across key databases targeted studies January 2023 to 2024, emphasizing recent insights into spread clinical impact. Findings reveal that exhibits higher infectivity evasion than previous variants, largely due L4555 mutation. From November March showed an increasing trend transmission. Previously approved antivirals, including Paxlovid, Veklury, Lagevrio, demonstrate effectiveness against JN.1, current vaccines still protect severe illness this variant. rates remain low. Monitoring efforts include genomic assessments, wastewater surveillance, digital tracking contain variant's spread. It essential encourage public maintain preventive measures reduce Continued research critical for understanding managing evolving landscape emerging variants.

Language: Английский

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A distribution-guided Mapper algorithm

BMC Bioinformatics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 5, 2025

The Mapper algorithm is an essential tool for exploring the data shape in topological analysis. With a dataset as input, outputs graph representing features of whole dataset. This often regarded approximation Reeb classic uses fixed interval lengths and overlapping ratios, which might fail to reveal subtle dataset, especially when underlying structure complex. In this work, we introduce distribution-guided named D-Mapper, utilizes property probability model intrinsic characteristics generate density-guided covers provide enhanced features. Moreover, metric accounting both quality overlap clustering extended persistent homology measure performance Mapper-type algorithms. Our numerical experiments indicate that D-Mapper outperforms various scenarios. We also apply SARS-COV-2 coronavirus RNA sequence explore different virus variants. results can vertical horizontal evolutionary processes viruses. code available at https://github.com/ShufeiGe/D-Mapper . from based on model. work demonstrates power fusing probabilistic models with

Language: Английский

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Recent SARS-CoV-2 evolution trajectories indicate the emergence of Omicron’s several subvariants and the current rise of KP.3.1.1 and XEC

Virology, Journal Year: 2025, Volume and Issue: unknown, P. 110508 - 110508

Published: March 1, 2025

Language: Английский

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Role of glycosylation mutations at the N-terminal domain of SARS-CoV-2 XEC variant in immune evasion, cell-cell fusion, and spike stability

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, producing new variants that drive global disease 2019 surges. XEC, a recombinant of KS.1.1 and KP.3.3, contains T22N F59S mutations in the spike protein’s N-terminal domain (NTD). The mutation, similar DelS31 mutation KP.3.1.1, introduces potential N-linked glycosylation site XEC. In this study, we examined neutralizing antibody (nAb) response effects sera from bivalent-vaccinated healthcare workers, BA.2.86/JN.1 wave-infected patients, XBB.1.5 monovalent-vaccinated hamsters, assessing responses XEC alongside D614G, JN.1, KP.3, KP.3.1.1. demonstrated significantly reduced neutralization titers across all cohorts, largely due mutation. Notably, removal sites KP.3.1.1 substantially restored nAb titers. Antigenic cartography analysis revealed be more antigenically distinct its common ancestral compared with as determining factor. Similar showed cell-cell fusion relative parental change attributed glycosylation. We also observed S1 shedding for which was reversed by ablation mutations, respectively. Molecular modeling suggests alter hydrophobic interactions adjacent protein residues, impacting both conformational stability neutralization. Overall, our findings underscore pivotal role NTD shaping SARS-CoV-2 biology immune escape mechanisms. IMPORTANCE continuous evolution severe has led emergence novel enhanced evasion properties, posing challenges current vaccination strategies. This study identifies key (NTD) particularly recent variant, impacts antigenicity, neutralization, stability. introduction an through T22N, along antigenic shift driven F59S, highlights how subtle can drastically viral recognition. By demonstrating restores sensitivity, work provides crucial insights into molecular mechanisms governing escape. Additionally, on contribute broader understanding variant fitness transmissibility. These emphasize importance monitoring emerging lineages support need adaptive vaccine designs counteract ongoing evolution.

Language: Английский

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From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

The worldwide spread of new SARS-CoV-2 variants emphasizes the need to diversify existing therapeutic strategies. TMPRSS2, a host protease crucial for entry, has garnered significant research attention as potential target intervention. Here, we optimized N-0385, previously reported TMPRSS2 ketobenzothiazole-based peptidomimetic inhibitor, by screening 135 derivatives affinity and antiviral potency. Among top candidates, N-0695 exhibited low nanomolar Ki values against three TTSPs associated with respiratory virus entry: matriptase, TMPRSS13. Notably, N-0920 demonstrated exceptional potency in reducing EG.5.1 JN.1 entry Calu-3 cells, representing first cellulo picomolar inhibitor EC50 300 90 pM, respectively. Additionally, molecular modeling provided insights into binding interactions between compounds their targets. This study underscores effectiveness our approach refining an scaffold enhance selectivity activity.

Language: Английский

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A Versatile High‐Throughput Single‐Cell Screening Platform for Profiling Antigen‐Specific Long‐Lived B Cells in Blood and Bone Marrow

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Antigen‐specific B cells play a crucial role in the long‐term immune response following infection or vaccination, differentiating into antibody‐secreting (ASCs) and memory (MBCs). However, profiling ASCs is challenging primarily due to their lack of membrane‐bound surface cell receptors. In this study, Modular Superhydrophobic Microwell Array Chip (MoSMAR‐chip) introduced as versatile, cost‐effective, high‐throughput platform for identifying characterizing individual antigen‐specific MBCs at single‐cell level within seven days. Using platform, comprehensive analyses single could be performed from bone marrows coronavirus disease 2019 (COVID‐19) vaccine‐immunized mice diverse set antibodies capable neutralizing highly divergent JN1 variant severe acute respiratory syndrome 2 (SARS‐CoV‐2) were identified. These results demonstrate that MoSMAR‐chip facilitates efficient multi‐omics functional ASCs, offering powerful tool investigating complex immunity clinical conditions, such infectious diseases, autoimmunity, beyond.

Language: Английский

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5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells

Virus Research, Journal Year: 2025, Volume and Issue: 356, P. 199578 - 199578

Published: April 23, 2025

Baicalin, a bioactive flavone found in Scutellaria baicalensis Georgi has anti-SARS-CoV-2 infection by targeting viral 3C-like protease (3CLpro). However, little is known about the antiviral activity of its 7-deoxy analogue, 5,6-dihydroxyflavone (5,6-DHF), especially against betacoronaviruses (beta-CoVs). We that 5,6-DHF exhibited more potent Omicron variant EG.5.1.1 than baicalein microneutralization test (MNT) and plaque reduction neutralization (PRNT). 5,6-Dihydroxyl (catechol) groups at A ring essential for suppression on SARS-CoV-2 because blocking them with methyl or methylene obsolesce activity. 3CLpro inhibition assay showed distinctive baicalein. Time addition test, molecular docking spike-bearing pseudotyped virus entry suggested interferes spike-ACE2 interaction receptor binding domain (RBD) spike hence inhibits replication. In to EG.5.1.1, was also effective another common human beta-CoVs, HCoV-OC43, their host cells. Taken together, present study demonstrated potential function as therapeutic candidate beta-CoVs.

Language: Английский

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B cell maturation restored ancestral germlines to control Omicron BA.2.86

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

ABSTRACT The unceasing interplay between SARS-CoV-2 and the human immune system has led to a continuous maturation of virus B cell response providing an opportunity track their evolution in real time. We longitudinally analyzed functional activity almost 1,000 neutralizing monoclonal antibodies (nAbs) isolated from vaccinated people, individuals with hybrid super immunity (SH), developed after three mRNA vaccine doses two breakthrough infections. most potent neutralization Fc functions against highly mutated variants, including BA.2.86, were found SH cohort. Despite different priming, epitope mapping revealed convergent antibody response. Neutralization was mainly driven by Class 1/2 nAbs while induced 3/4 antibodies. Remarkably, broad mediated restored IGHV3-53/3-66 germlines which, heterogenous exposure S proteins, increased level somatic hypermutations. Our study shows resilience which previously expanded activated naïve cells broaden repertoire control future variants.

Language: Английский

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Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 11, 2024

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received bivalent mRNA vaccine booster, patients infected during BA.2.86/JN.1-wave, hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that shows much less nAb escape from WT-BA.4/5 JN.1-wave breakthrough infection sera compared JN.1 XBB.1.5. Interestingly. is more resistant by XBB.15-monovalent-vaccinated hamster than BA.2.86/JN.1 XBB.1.5, but efficiently neutralized class III monoclonal S309, which largely fails neutralize BA.2.86/JN.1. Importantly, exhibits higher levels fusion activity, furin cleavage efficiency Antigenically, closer ancestral BA.2 other recently Omicron subvariants Altogether, these results highlight immune properties as well biology new underscore importance continuous surveillance informed decision-making development effective vaccines.

Language: Английский

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