SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Nature Microbiology, Год журнала: 2022, Номер 7(8), С. 1161 - 1179

Опубликована: Июль 7, 2022

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone public health response to COVID-19. The emergence hypermutated, increasingly transmissible variants concern (VOCs) threaten this strategy. Omicron (B.1.1.529), fifth VOC be described, harbours multiple amino acid mutations in spike, half which lie within receptor-binding domain. Here we demonstrate substantial evasion neutralization by BA.1 and BA.2 vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 mRNA-1273. These data were mirrored reduction real-world vaccine effectiveness that was partially restored booster vaccination. did not induce cell syncytia favoured TMPRSS2-independent endosomal entry pathway, these phenotypes mapping distinct regions protein. Impaired fusion determined domain, while mapped S2 Such marked changes antigenicity replicative biology may underlie rapid global spread altered pathogenicity variant.

Язык: Английский

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SARS-CoV-2 Omicron variant: recent progress and future perspectives

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Апрель 28, 2022

Abstract Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there have been a few variants severe acute respiratory syndrome 2 (SARS-CoV-2), one which is Omicron variant (B.1.1.529). The most mutated SARS-CoV-2 variant, and its high transmissibility immune evasion ability raised global concerns. Owing to enhanced transmissibility, has rapidly replaced Delta as dominant in several regions. However, recent studies shown that exhibits reduced pathogenicity due altered cell tropism. In addition, significant resistance neutralizing activity vaccines, convalescent serum, antibody therapies. present review, advances molecular clinical characteristics infectivity, pathogenicity, was summarized, potential therapeutic applications response infection were discussed. Furthermore, we highlighted future waves strategies end pandemic.

Язык: Английский

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Therapeutic strategies for COVID-19: progress and lessons learned

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(6), С. 449 - 475

Опубликована: Апрель 19, 2023

Язык: Английский

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SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells

Emerging Microbes & Infections, Год журнала: 2021, Номер 11(1), С. 277 - 283

Опубликована: Дек. 24, 2021

The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it >50 mutations, many of which are known to affect transmissibility or cause immune escape. In this study, we sought investigate the virological characteristics compared with Delta dominated world since mid-2021. replicated more slowly than transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, well Calu3 cell line robust TMPRSS2 expression, while poorly line. Competition assay showed that outcompeted VeroE6/TMPRSS2 To confirm difference entry pathway between variants, assessed antiviral effect bafilomycin A1, chloroquine (inhibiting endocytic pathway), camostat pathway). Camostat potently inhibited but not variant, A1 could inhibit both variants. Moreover, also weaker cell-cell fusion activity when Collectively, our results suggest infection is enhanced by largely mediated via pathway. variants may have an implication on clinical manifestations disease severity.

Язык: Английский

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Structural biology of SARS-CoV-2: open the door for novel therapies

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Янв. 27, 2022

Abstract Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of pandemic disease COVID-19, which so far without efficacious treatment. The discovery therapy reagents for treating COVID-19 are urgently needed, and structures potential drug-target proteins in viral life cycle particularly important. SARS-CoV-2, a member Orthocoronavirinae subfamily containing largest RNA genome, encodes 29 including nonstructural, structural accessory involved adsorption, entry uncoating, nucleic acid replication transcription, assembly release, etc. These individually act as partner machinery or forming complexes with host cellular factors to participate essential physiological activities. This review summarizes representative typically agents that target SARS-CoV-2 some critical pathogenesis, providing insights into mechanisms underlying infection, prevention Indeed, these studies open door COVID therapies, leading ways prevent treat especially, treatment caused by variants imperative.

Язык: Английский

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Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases

Gastroenterology, Год журнала: 2022, Номер 163(2), С. 495 - 506.e8

Опубликована: Май 1, 2022

Язык: Английский

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Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis

Trends in Molecular Medicine, Год журнала: 2022, Номер 28(7), С. 542 - 554

Опубликована: Апрель 21, 2022

Язык: Английский

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Broadly neutralizing antibodies target the coronavirus fusion peptide

Science, Год журнала: 2022, Номер 377(6607), С. 728 - 735

Опубликована: Июль 12, 2022

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach identify six monoclonal antibodies that bind spike proteins from all seven human-infecting coronaviruses. All conserved fusion peptide region adjacent S2' cleavage site. COV44-62 and COV44-79 neutralize alpha- betacoronaviruses, including severe acute respiratory syndrome 2 (SARS-CoV-2) Omicron subvariants BA.2 BA.4/5, albeit with lower potency than receptor binding domain-specific antibodies. In crystal structures antigen-binding fragments SARS-CoV-2 peptide, epitope adopts a helical structure includes arginine residue at limited disease caused by in Syrian hamster model. These findings highlight as candidate next-generation vaccine development.

Язык: Английский

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A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

Nature, Год журнала: 2022, Номер 605(7909), С. 340 - 348

Опубликована: Март 28, 2022

The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced owing to emerging variants of concern

Язык: Английский

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Innate immune evasion strategies of SARS-CoV-2

Nature Reviews Microbiology, Год журнала: 2023, Номер unknown

Опубликована: Янв. 11, 2023

Язык: Английский

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