Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 13, 2024

Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicate IGROV-1 no longer Vero E6 are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhances NAb against both BA.2.86 displays affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Язык: Английский

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Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Immunity, Год журнала: 2023, Номер 56(3), С. 669 - 686.e7

Опубликована: Фев. 16, 2023

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and more effectively respond SARS-CoV-2 variants. The emergence of Omicron subvariants illustrates limitations solely targeting receptor-binding domain (RBD) spike (S) protein. Here, we isolated a large panel (bnAbs) from recovered-vaccinated donors, which targets conserved S2 region in betacoronavirus fusion machinery. Select bnAbs showed broad vivo protection all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, MERS-CoV, have spilled over into humans past two decades. Structural studies these delineated molecular basis for their reactivity revealed common antibody features targetable by vaccination strategies. These provide new insights opportunities antibody-based interventions pan-betacoronavirus vaccines.

Язык: Английский

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The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

MedComm, Год журнала: 2023, Номер 4(2)

Опубликована: Март 15, 2023

As the fifth variant of concern SARS-CoV-2 virus, Omicron (B.1.1.529) has quickly become dominant type among previous circulating variants worldwide. During wave, several subvariants have emerged, with some exhibiting greater infectivity and immune evasion, accounting for their fast spread across many countries. Recently, two subvariants, BQ.1 XBB lineages, including BQ.1.1, XBB.1, XBB.1.5, a global public health issue given ability to escape from therapeutic monoclonal antibodies herd immunity induced by prior coronavirus disease 2019 (COVID-19) vaccines, boosters, infection. In this respect, which been established harbor rare mutation F486P, demonstrates superior transmissibility compared other emerged as strain in This review provides comprehensive overview epidemiological features, spike mutations, evasion lineages. We expounded on mechanisms underlying mutations neutralizing vaccinated or convalescent COVID-19 individuals (mAbs) proposed strategies prevention against sublineages.

Язык: Английский

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SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency

Cell, Год журнала: 2024, Номер 187(3), С. 596 - 608.e17

Опубликована: Янв. 8, 2024

Язык: Английский

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TMPRSS2 is a functional receptor for human coronavirus HKU1

Nature, Год журнала: 2023, Номер 624(7990), С. 207 - 214

Опубликована: Окт. 25, 2023

Язык: Английский

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Duration of protection of ancestral-strain monovalent vaccines and effectiveness of bivalent BA.1 boosters against COVID-19 hospitalisation in England: a test-negative case-control study

The Lancet Infectious Diseases, Год журнала: 2023, Номер 23(11), С. 1235 - 1243

Опубликована: Июль 12, 2023

Bivalent BA.1 booster vaccines were offered to adults aged 50 years or older and clinically vulnerable people as part of the 2022 autumn COVID-19 vaccination programme in England. Previously, all England had been a primary course consisting two doses either ChAdOx1-S monovalent mRNA vaccine an vaccine. We aimed estimate long-term duration protection provided by vaccines, incremental effectiveness bivalent boosters.In this test-negative case-control study, cases controls 18 identified from national data for PCR tests done hospital settings Our analysis was restricted with acute respiratory infections coded diagnosis field. Data status extracted English register linked testing data. Between June 13 Dec 25, 2022, we estimated against hospitalisation three more compared being unvaccinated, stratified age (18-64 vs ≥65 years). Sept 5, Feb 2023, (ie, addition earlier vaccines) receiving at least (when last dose 6 months ago) among older. Analyses adjusted week test, gender, age, risk group, residing care home, health social worker, Index Multiple Deprivation quintile, ethnicity, recent positivity.Our included 19 841 43 410 controls. Absolute who received plateaued after around 50% those 65 30% 18-64 years. analyses boosters 9954 39 108 Incremental peaked 53·0% (95% CI 47·9-57·5) 2-4 weeks administration, before waning 35·9% (31·4-40·1) 10 weeks.Our study provides evidence that offer moderate effective preventing time when omicron lineages circulating England.None.

Язык: Английский

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Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

Protein & Cell, Год журнала: 2024, Номер 15(6), С. 403 - 418

Опубликована: Март 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Язык: Английский

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Longitudinal outcomes of COVID-19 in solid organ transplant recipients from 2020 to 2023

American Journal of Transplantation, Год журнала: 2024, Номер 24(7), С. 1303 - 1316

Опубликована: Март 17, 2024

Data regarding coronavirus disease 2019 (COVID-19) outcomes in solid organ transplant recipients (SOTr) across severe acute respiratory syndrome 2 (SARS-CoV-2) waves, including the impact of different measures, are lacking. This cohort study, conducted from March 2020 to May 2023 Toronto, Canada, aimed analyze COVID-19 1975 SOTr various SARS-CoV-2 waves and assess preventive treatment measures. The primary outcome was COVID-19, defined as requiring supplemental oxygen, with secondary hospitalization, length stay, intensive care unit (ICU) admission, 30-day 1-year all-cause mortality. were categorized Wildtype/Alpha/Delta (318 cases, 16.1%), Omicron BA.1 (268, 26.2%), BA.2 13.6%), BA.5 (561, 28.4%), BQ.1.1 (188, 9.5%), XBB.1.5 (123, 6.2%). Severe rate highest during wave (44.6%), lower (5.7%-16.1%). Lung transplantation associated (OR: 4.62, 95% CI: 2.71-7.89), along rituximab 4.24, 1.04-17.3), long-term corticosteroid use 3.11, 1.46-6.62), older age 1.51, 1.30-1.76), chronic lung 2.11, 1.36-3.30), kidney 2.18, 1.17-4.07), diabetes 1.97, 1.37-2.83). Early ≥3 vaccine doses reduced severity 0.29, 0.19-0.46, 0.35, 0.21-0.60, respectively). Tixagevimab/cilgavimab bivalent boosters did not show a significant impact. study concludes that decreased variants SOTr. worse may benefit more early therapeutic interventions.

Язык: Английский

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SARS-CoV-2 Drug Resistance and Therapeutic Approaches

Heliyon, Год журнала: 2025, Номер 11(2), С. e41980 - e41980

Опубликована: Янв. 1, 2025

Язык: Английский

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Receptor-binding proteins from animal viruses are broadly compatible with human cell entry factors

Nature Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Abstract Cross-species transmission of animal viruses poses a threat to human health. However, systematic experimental assessments these risks remain scarce. A critical step in viral infection is cellular internalization mediated by receptor-binding proteins (RBPs). Here we constructed pseudotypes bearing the RBPs 102 enveloped RNA and assayed their infectivity across 5,202 RBP–cell combinations. This showed that most tested have potential enter cells. Pseudotype varied widely among 14 families examined was influenced RBP characteristics, host origin target cell type. Cellular gene expression data revealed availability specific cell-surface receptors not necessarily main factor limiting entry additional factors must be considered. Altogether, results suggest weak interspecies barriers early stages advance our understanding molecular interactions driving zoonosis.

Язык: Английский

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