Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant DOI Creative Commons
Shuhei Tsujino, Sayaka Deguchi, Tomo Nomai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 21, 2023

Abstract In middle-late 2023, a sublineage of SARS-CoV-2 Omicron XBB, EG.5.1 (a progeny XBB.1.9.2), is spreading rapidly around the world. Here, we performed multiscale investigations to reveal virological features newly emerging variant. Our phylogenetic-epidemic dynamics modeling suggested that two hallmark substitutions EG.5.1, S:F456L and ORF9b:I5T, are critical increased viral fitness. Experimental addressing growth kinetics, sensitivity clinically available antivirals, fusogenicity pathogenicity comparable XBB.1.5. However, cryo-electron microscopy reveals structural difference between spike proteins We further assessed impact ORF9b:I5T on features, but it was almost negligible at least in our experimental setup. provide knowledge for understanding evolution trait pathogenic viruses human population.

Language: Английский

Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants DOI Creative Commons
Tomokazu Tamura, Jumpei Ito,

Keiya Uriu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 16, 2023

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that emerged through recombination of two cocirculating BA.2 lineages, BJ.1 BM.1.1.1 (a progeny BA.2.75), during summer 2022. XBB.1 variant most profoundly resistant to BA.2/5 breakthrough infection sera date more fusogenic than BA.2.75. The breakpoint located in receptor-binding domain spike, each region recombinant spike confers immune evasion increases fusogenicity. We further provide structural basis for interaction between human ACE2. Finally, intrinsic pathogenicity male hamsters comparable or even lower multiscale investigation provides evidence suggesting first observed increase its fitness rather substitutions.

Language: Английский

Citations

261
Virological characteristics of the SARS-CoV-2 JN.1 variant DOI Open Access

Yu Kaku,

Kaho Okumura, Miguel Padilla‐Blanco

et al.

The Lancet Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(2), P. e82 - e82

Published: Jan. 3, 2024

Language: Английский

Citations

210
Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant DOI Creative Commons
Jumpei Ito, Rigel Suzuki,

Keiya Uriu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 11, 2023

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including R346, K444, L452, N460, F486. Here, we characterize convergent evolution of properties one recent lineage concern, BQ.1.1. Our phylogenetic analysis suggests that these five are recurrently acquired, particularly younger lineages. Epidemic dynamics modelling increase viral fitness, a large proportion fitness variation within lineages can be explained by substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 BA.5 infection sera more efficiently, as demonstrated neutralization assays. The pathogenicity hamsters is lower than BA.5. multiscale investigations illuminate evolutionary rules governing for known 2022.

Language: Английский

Citations

121
The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants DOI Creative Commons
Danyi Ao, Xuemei He, Weiqi Hong

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(2)

Published: March 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.

Language: Английский

Citations

109
Virological characteristics of the SARS-CoV-2 BA.2.86 variant DOI Creative Commons
Tomokazu Tamura,

Keita Mizuma,

Hesham Nasser

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(2), P. 170 - 180.e12

Published: Jan. 26, 2024

In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct lineage, the BA.2.86 variant, also emerged. is phylogenetically from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined virological characteristics of variant. Our epidemic dynamics modeling suggested that relative reproduction number significantly higher than EG.5.1. Additionally, four clinically available antivirals effective against BA.2.86. Although fusogenicity similar to parental BA.2 spike, intrinsic pathogenicity hamsters was lower BA.2. Since growth kinetics are those both vitro and vivo, attenuated likely due decreased replication capacity. These findings uncover features BA.2.86, providing insights for control treatment.

Language: Английский

Citations

63
Antiviral efficacy of the SARS-CoV-2 XBB breakthrough infection sera against omicron subvariants including EG.5 DOI Open Access

Yu Kaku,

Yusuke Kosugi,

Keiya Uriu

et al.

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(10), P. e395 - e396

Published: Sept. 11, 2023

Language: Английский

Citations

53
Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant DOI Creative Commons
Tomokazu Tamura, Takashi Irie, Sayaka Deguchi

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 8, 2024

Abstract Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence XBB.1.5, a new Variant Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring S486P spike (S) mutation, subsequent to acquisition nonsense mutation ORF8. Neutralization assays showed similar abilities immune escape between and XBB.1. We determine structural basis for interaction human ACE2 S protein showing overall structures proteins XBB.1.5. provide intrinsic pathogenicity hamsters. Importantly, we find ORF8 impairment MHC suppression. In vivo experiments using recombinant viruses reveal mutations are involved with reduced virulence Together, our study identifies two viral functions defined difference

Language: Английский

Citations

49
Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants DOI Creative Commons
Ann‐Kathrin Reuschl, Lucy Thorne, Matthew Whelan

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(2), P. 451 - 463

Published: Jan. 16, 2024

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve globally dominant subvariants. Here we compared their replication cell lines and primary airway cultures measured host responses infection. We discovered that subvariants BA.4 BA.5 have improved suppression innate immunity when earlier BA.1 BA.2. Similarly, more recent (BA.2.75 XBB lineages) also triggered reduced immune activation. This correlated increased expression viral antagonists Orf6 nucleocapsid, reminiscent VOCs Alpha Delta. Increased levels suppressed infection by decreasing IRF3 STAT1 signalling transcription factor phosphorylation nuclear translocation. Our data suggest convergent evolution antagonist a common pathway link subvariant dominance evasion.

Language: Английский

Citations

45
Safety and Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine in Individuals ≥12 Years Old: A Phase 2/3 Trial DOI Creative Commons

Juleen Gayed,

Oyeniyi Diya,

Francine S. Lowry

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 118 - 118

Published: Jan. 24, 2024

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of ongoing, open-label, phase 2/3 study monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy participants ≥12 years old (N = 412 (12–17 years, N 30; 18–55 174; >55 208)) who previously received ≥3 doses US-authorized mRNA vaccine, the most recent being BA.4/BA.5-adapted bivalent vaccine ≥150 days before vaccination, were vaccinated. Serum 50% neutralizing titers XBB.1.5, EG.5.1, BA.2.86 measured 7 1 month after vaccination in subset ≥18-year-olds 40) positive for SARS-CoV-2 at baseline. Seven-day was also evaluated matched group previous (ClinicalTrials.gov Identifier: NCT05472038). There no new signals; local reactions systemic events mostly mild to moderate severity, adverse infrequent, none led withdrawal. The induced numerically higher than robust responses all three sublineages month. These support favorable benefit-risk profile 30 μg. ClinicalTrials.gov NCT05997290

Language: Английский

Citations

24
Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion DOI Creative Commons

Song Xue,

Yuru Han, Fan Wu

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(6), P. 403 - 418

Published: March 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.

Language: Английский

Citations

21