SARS-CoV-2 variant biology: immune escape, transmission and fitness

Nature Reviews Microbiology, Год журнала: 2023, Номер unknown

Опубликована: Янв. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Язык: Английский

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Spike deep mutational scanning helps predict success of SARS-CoV-2 clades

Nature, Год журнала: 2024, Номер 631(8021), С. 617 - 626

Опубликована: Июль 3, 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion

Язык: Английский

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Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic

Nature Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Abstract SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging comprehensively compare many spikes that emerged during pandemic a single experimental platform. Here we generated panel recombinant viruses carrying different proteins from 27 circulating between 2020 and 2024 same genomic background. We then assessed several phenotypic traits both vitro vivo. found distinct among before after emergence Omicron variants. Spike post-Omicron maintained enhanced tropism for nasal epithelium large airways but displayed, over time, typical pre-Omicron Hence, with features pre- may continue emerge future.

Язык: Английский

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Molecular insights into the adaptive evolution of SARS-CoV-2 spike protein

Journal of Infection, Год журнала: 2024, Номер 88(3), С. 106121 - 106121

Опубликована: Фев. 16, 2024

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has substantially damaged global economy and human health. spike (S) protein of coronaviruses plays a pivotal role in viral entry binding to host cell receptors. Additionally, it acts as primary target for neutralizing antibodies those infected is central focus currently utilized or researched vaccines. During virus's adaptation host, S SARS-CoV-2 undergone significant evolution. As pandemic unfolded, new mutations have arisen vanished, giving rise distinctive amino acid profiles within variant concern strains SARS-CoV-2. Notably, many these changes been positively selected, leading substantial alterations characteristics, such heightened transmissibility immune evasion capabilities. This review aims provide an overview our current understanding structural implications associated with key These research findings shed light on intricate dynamic nature evolution, underscoring importance continuous monitoring analysis genomes. Through molecular-level investigations, we can attain deeper insights into adaptive offering valuable guidance designing vaccines developing antiviral drugs combat ever-evolving threats.

Язык: Английский

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Architects of infection: A structural overview of SARS-related coronavirus spike glycoproteins

Virology, Год журнала: 2025, Номер unknown, С. 110383 - 110383

Опубликована: Янв. 1, 2025

The frequency of zoonotic viral emergence within the Coronaviridae family highlights critical need to understand structural features spike proteins that govern entry and host adaptation. Investigating conservation variation in key regions protein-those involved range, binding affinity, entry, immune evasion-is essential for predicting evolutionary pathways coronaviruses, assessing risk future host-jumping events, discovering pan-neutralising antibodies. Here we summarise our current understanding similar SARS-CoV-2 from compare functional similarities differences. Our aim is demonstrate significant sequence between a range species outline importance animal coronavirus surveillance investigation endeavour pandemic preparedness against emerging viruses.

Язык: Английский

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Evolutionary remodelling of N‐terminal domain loops fine‐tunes SARS‐CoV‐2 spike

EMBO Reports, Год журнала: 2022, Номер 23(10)

Опубликована: Авг. 24, 2022

The emergence of SARS-CoV-2 variants has exacerbated the COVID-19 global health crisis. Thus far, all carry mutations in spike glycoprotein, which is a critical determinant viral transmission being responsible for attachment, receptor engagement and membrane fusion, an important target immunity. Variants frequently bear truncations flexible loops N-terminal domain (NTD) spike; functional importance these modifications remained poorly characterised. We demonstrate that NTD deletions are efficient entry by Alpha Omicron this correlates with stability. Phylogenetic analysis reveals extensive loop length polymorphisms across sarbecoviruses, setting evolutionary precedent remodelling. Guided analyses, we variations length, alone, sufficient to modulate virus entry. propose act fine-tune may provide mechanism navigate complex selection landscape encompassing optimisation essential functionality, immune-driven antigenic variation ongoing adaptation new host.

Язык: Английский

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Coordinated evolution at amino acid sites of SARS-CoV-2 spike

eLife, Год журнала: 2023, Номер 12

Опубликована: Фев. 2, 2023

SARS-CoV-2 has adapted in a stepwise manner, with multiple beneficial mutations accumulating rapid succession at origins of VOCs, and the reasons for this are unclear. Here, we searched coordinated evolution amino acid sites spike protein SARS-CoV-2. Specifically, concordantly evolving site pairs (CSPs) which changes one were rapidly followed by other same lineage. We detected 46 formed 45 CSP. Sites CSP closer to each structure than random pairs, indicating that concordant functional basis. Notably, carrying lineage defining four VOCs circulated before May 2021 enriched CSPs. For Alpha VOC, enrichment is even if sequences removed from analysis, VOC origin could have been facilitated positive epistasis. Additionally, nine discordantly where unexpectedly rarely occurred on background specific allele another site, example wild-type D 614 (four pairs) or derived Y 501 (three pairs). Our findings hint epistasis between delayed assembly advantageous combinations comprising least some VOCs.

Язык: Английский

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Deep mutagenesis scanning using whole trimeric SARS-CoV-2 spike highlights the importance of NTD-RBD interactions in determining spike phenotype

PLoS Pathogens, Год журнала: 2023, Номер 19(8), С. e1011545 - e1011545

Опубликована: Авг. 3, 2023

New variants of SARS-CoV-2 are continually emerging with mutations in spike associated increased transmissibility and immune escape. Phenotypic maps can inform the prediction concerning from genomic surveillance, however most these currently derive studies using monomeric RBD, while is trimeric, contains additional domains. These may fail to reflect interdomain interactions phenotypes. To try improve on this, we developed a platform for deep mutational scanning whole trimeric spike. We confirmed previously reported epistatic effect within RBD affecting ACE2 binding, that highlights importance updating base sequence future studies. Using post vaccine sera, found response vaccinated individuals was highly focused one or two epitopes single point at positions account escape mediated by Omicron BA.1 RBD. However, unexpectedly alone does not high level antigenic show NTD amplifies evasion its reduces neutralistion directed monoclonal antibodies, impacts interaction. variation thus an important mechanism SARS-CoV-2. Such effects seen when pre-stabilized proteins used, suggesting require protein mobility express their phenotype.

Язык: Английский

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Subsequent Waves of Convergent Evolution in SARS-CoV-2 Genes and Proteins

Vaccines, Год журнала: 2024, Номер 12(8), С. 887 - 887

Опубликована: Авг. 5, 2024

Beginning in 2022, following widespread infection and vaccination among the global population, SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines past infections. This review covers convergent evolution of structural, nonstructural, accessory proteins SARS-CoV-2, with a specific look at common mutations found long-lasting infections that hint potentially reverting an enteric sarbecovirus type.

Язык: Английский

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Jointly modeling deep mutational scans identifies shifted mutational effects among SARS-CoV-2 spike homologs

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 2, 2023

Deep mutational scanning (DMS) is a high-throughput experimental technique that measures the effects of thousands mutations to protein. These experiments can be performed on multiple homologs protein or same selected under conditions. It often biological interest identify with shifted across However, it challenging determine if observed shifts arise from signal noise. Here, we describe method for jointly inferring DMS while also identifying have in their among experiments. A key aspect our regularize inferred shifts, so they are nonzero only when strongly supported by data. We apply this measure how spike proteins SARS-CoV-2 variants (Delta, Omicron BA.1, and BA.2) affect cell entry. Most conserved between these homologs, but fraction markedly shifted. experimentally validate subset effects, confirm differences > 1,000-fold impact mutation spike-mediated viral infection spikes different variants. Overall, work establishes general approach comparing sets biologically important effects.

Язык: Английский

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