Origin, virological features, immune evasion and intervention of SARS-CoV-2 Omicron sublineages

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

Опубликована: Июль 19, 2022

Recently, a large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continuously emerged and posed major threat to global public health. Among them, particularly, Omicron variant (B.1.1.529), first identified in November 2021, carried numerous mutations its spike protein (S), then quickly spread around the world. Currently, has expanded into more than one hundred sublineages, such as BA.1, BA.2, BA.2.12.1, BA.4 BA.5, which have already become globally dominant variants. Different from other concern (VOCs) SARS-CoV-2, sublineages exhibit increased transmissibility immune escape neutralizing antibodies generated through previous infection or vaccination, caused re-infections breakthrough infections. In this prospective, we focused on origin, virological features, evasion intervention will benefit development next-generation vaccines therapeutics, including pan-sarbecovirus universal anti-CoV combat currently circulating future emerging well SARS-CoV-2

Язык: Английский

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Immune Escape Associated with RBD Omicron Mutations and SARS-CoV-2 Evolution Dynamics

Viruses, Год журнала: 2022, Номер 14(8), С. 1603 - 1603

Опубликована: Июль 22, 2022

The evolution and the emergence of new mutations viruses affect their transmissibility and/or pathogenicity features, depending on different evolutionary scenarios virus adaptation to host. A typical trade-off scenario SARS-CoV-2 has been proposed, which leads appearance an Omicron strain with lowered lethality, yet enhanced transmissibility. This direction might be partly explained by therapeutic agents escape from vaccine-induced natural immunity formed other strains. Omicron's high mutation rate in Spike protein, as well its previously described genome (Kandeel et al., 2021), revealed a gap between it strains, indicating absence transitional form strain. Therefore, emerged serotype divergent lineage is rapidly evolving variant concern, whose subvariants continue manifest. Its further understanding monitoring key that provide immune affinity towards receptor could useful for vaccine development order control COVID-19 pandemic.

Язык: Английский

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SARS-CoV-2 Exposure in Norway Rats (Rattus norvegicus) from New York City

mBio, Год журнала: 2023, Номер 14(2)

Опубликована: Март 9, 2023

The host tropism expansion of SARS-CoV-2 raises concern for the potential risk reverse-zoonotic transmission emerging variants into rodent species, including wild rat species. In this study, we present both genetic and serological evidence exposure to New York City population, these viruses may be linked that were circulating during early stages pandemic.

Язык: Английский

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Markov State Models and Perturbation-Based Approaches Reveal Distinct Dynamic Signatures and Hidden Allosteric Pockets in the Emerging SARS-Cov-2 Spike Omicron Variant Complexes with the Host Receptor: The Interplay of Dynamics and Convergent Evolution Modulates Allostery and Functional Mechanisms

Journal of Chemical Information and Modeling, Год журнала: 2023, Номер 63(16), С. 5272 - 5296

Опубликована: Авг. 7, 2023

The new generation of SARS-CoV-2 Omicron variants displayed a significant growth advantage and increased viral fitness by acquiring convergent mutations, suggesting that the immune pressure can promote evolution leading to sudden acceleration evolution. In current study, we combined structural modeling, microsecond molecular dynamics simulations, Markov state models characterize conformational landscapes identify specific dynamic signatures spike complexes with host receptor ACE2 for recently emerged highly transmissible XBB.1, XBB.1.5, BQ.1, BQ.1.1 variants. Microsecond simulations Markovian modeling provided detailed characterization functional states revealed thermodynamic stabilization XBB.1.5 subvariant, which be contrasted more BQ.1 subvariants. Despite considerable similarities, mutations induce unique distributions states. results suggested variant-specific changes mobility in interfacial loops receptor-binding domain protein fine-tuned through crosstalk between could provide an evolutionary path modulation escape. By combining atomistic analysis perturbation-based approaches, determined important complementary roles mutation sites as effectors receivers allosteric signaling involved plasticity regulation communications. This study also hidden pockets control distribution flexible adaptable regions.

Язык: Английский

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Structural basis for receptor binding and broader interspecies receptor recognition of currently circulating Omicron sub-variants

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 21, 2023

Abstract Multiple SARS-CoV-2 Omicron sub-variants, such as BA.2, BA.2.12.1, BA.4, and BA.5, emerge one after another. BA.5 has become the dominant strain worldwide. Additionally, BA.2.75 is significantly increasing in some countries. Exploring their receptor binding interspecies transmission risk urgently needed. Herein, we examine capacities of human other 28 animal ACE2 orthologs covering nine orders towards S proteins these sub-variants. The affinities between hACE2 sub-variants remain range that previous variants concerns (VOCs) or interests (VOIs). Notably, R493Q reverse mutation enhances bindings ACE2s from humans many animals closely related to life, suggesting an increased cross-species transmission. Structures S/hACE2 RBD/hACE2 complexes for BA.2 mouse, rat golden hamster are determined reveal molecular basis broader recognition.

Язык: Английский

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Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein

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

Опубликована: Фев. 29, 2024

Abstract The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success stems from mutations within its spike glycoprotein, causing immune evasion enhanced receptor binding. We present binding studies demonstrate retention contacts with human ACE2 striking decrease in to mouse due revertant R493Q mutation. Despite extensive antibody binding, we highlight region on protein domain (RBD) is recognized by serum antibodies donor hybrid immunity, collected prior emergence variant. T cell assays reveal frequencies spike-specific CD4 + CD8 cells amongst donors skewed towards Th1 phenotype having attenuated effector cytokine secretion as compared ancestral protein-specific cells. Thus, while retained efficient gained antigenic alterations, it remains susceptible recognition induced via vaccination infection.

Язык: Английский

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Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2

The Journal of Immunology, Год журнала: 2025, Номер 214(1), С. 115 - 129

Опубликована: Янв. 1, 2025

Abstract As one of the earliest identified susceptible animals for SARS-CoV-2, cats are also vulnerable hosts feline coronaviruses, ie enteric coronavirus (FECV). Here, to understand cross-presentation coronavirus-derived peptides by cat major histocompatibility complex molecule leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented FLA-K*00701 and FLA-E*00301 were through elution further confirmed structural determination 2 FLA I molecules. Based on these precise peptides, atlas cross-presenting from different coronaviruses in sketched with 3 hotspots C-terminal half ORF1ab protein. The possibility is supported similar conformation corresponding KP-CoV-9 (RSFIEDLLF) KM-FECV-9 (RSAVEDLLF) FLA-K*00701. Our findings provide insights into understanding SARS-CoV-2 FECV development universal vaccine coronaviruses.

Язык: Английский

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Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses

EBioMedicine, Год журнала: 2022, Номер 86, С. 104341 - 104341

Опубликована: Ноя. 12, 2022

BackgroundThe COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein. "variants concern" have acquired mutations in this allowing them evade vaccine-induced humoral immunity. Recent approaches improve breadth protection beyond required use mixtures RBD antigens from different sarbecoviruses. It may therefore be beneficial develop vaccine which protective immune more conserved region S protein.MethodsHere we developed based on S2 subunit protein optimized adjuvant immunization regimen Syrian hamsters BALB/c mice. We characterized efficacy against variants other coronaviruses.FindingsImmunization with S2-based constructs elicited broadly cross-reactive IgG recognized proteins not only variants, but also SARS-CoV-1, four endemic human coronaviruses. Importantly, reduced virus titers respiratory tissues vaccinated animals challenged B.1.351 (beta), B.1.617.2 (delta), BA.1 (omicron) as well pangolin coronavirus.InterpretationThese results suggest can elicit resulting limited replication, thus providing framework for designing broad coronaviruses.FundingNIH, Japan Agency Medical Research Development, Garry Betty/ V Foundation Chair Fund, NSF.

Язык: Английский

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Omicron BA.1 and BA.2 variants increase the interactions of SARS-CoV-2 spike glycoprotein with ACE2

Journal of Molecular Graphics and Modelling, Год журнала: 2022, Номер 117, С. 108286 - 108286

Опубликована: Авг. 4, 2022

Язык: Английский

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Evolutionary rate of SARS-CoV-2 increases during zoonotic infection of farmed mink

Virus Evolution, Год журнала: 2023, Номер 9(1)

Опубликована: Янв. 1, 2023

Abstract To investigate genetic signatures of adaptation to the mink host, we characterised evolutionary rate heterogeneity in mink-associated severe acute respiratory syndrome coronaviruses (SARS-CoV-2). In 2020, first detected anthropozoonotic spillover event SARS-CoV-2 occurred farms throughout Europe and North America. Both spill-back lineages into human population spread surrounding wildlife were reported, highlighting potential formation a zoonotic reservoir. Our findings suggest that underwent an episodic increase upon introduction host before returning normal range observed humans. Furthermore, could have circulated for month detection, during this period, estimates between 3 × 10–3 1.05 10–2 (95 per cent HPD, with mean 6.59 10–3) four- thirteen-fold compared As there is evidence unique mutational patterns within lineages, explored emergence four mink-specific Spike protein amino acid substitutions Y453F, S1147L, F486L, Q314K. We found mutation Y453F emerged early multiple outbreaks mutations F486L Q314K may co-occur. undergoes brief, but considerable, response greater selective pressures species jumps, which lead occurrence mutations. These emphasise necessity ongoing surveillance infections future.

Язык: Английский

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