SARS-CoV-2 JN.1 reveals attenuated pathogenicity and airborne transmission DOI Creative Commons
Ruixue Liu,

Qiushi Jin,

Wenqi Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract JN.1 is a subvariant of SARS-CoV-2 Omicron BA.2.86 lineage that was predominant worldwide in early 2024, which the vivo characteristics are largely unknown. Our results demonstrated replication more efficient than parental BA.2 Vero cells, low dependence on TMPRSS2. Compared to variants and XBB EG.5.1, replicated less efficiently hACE2 mouse lungs intranasal infection not lethal mice led weaker immune dysregulation. On sensitive, aged hamster model, lower mortality rate no weight loss, corresponding well with preference airways. Lower amounts viruses nasal washes exhaled aerosols were detected infected wildtype hamsters consistently, also exhibited reduced airborne transmission. Moreover, poor transmission clearly even by using expressing receptors whole airway. Thus both pathogenicity be attenuated. Importance Currently, its subvariants have fully replaced previous dominant around world. Although strong evasion has been distinctly revealed, remained unclear. By multiple Omicron-sensitive rodent models, our findings The weak consistent reported relative transmissibility human, airway-expressing ulteriorly eliminates potential bias viral studies induced receptor divergence between animal models human. These uncover virological novel lineage, providing insights for communicable disease control.

Language: Английский

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

61
AlphaFold2 Modeling and Molecular Dynamics Simulations of the Conformational Ensembles for the SARS-CoV-2 Spike Omicron JN.1, KP.2 and KP.3 Variants: Mutational Profiling of Binding Energetics Reveals Epistatic Drivers of the ACE2 Affinity and Escape Hotspots of Antibody Resistance DOI Creative Commons
Nishank Raisinghani, Mohammed Alshahrani,

Grace Gupta

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1458 - 1458

Published: Sept. 13, 2024

The most recent wave of SARS-CoV-2 Omicron variants descending from BA.2 and BA.2.86 exhibited improved viral growth fitness due to convergent evolution functional hotspots. These hotspots operate in tandem optimize both receptor binding for effective infection immune evasion efficiency, thereby maintaining overall fitness. lack molecular details on structure, dynamics energetics the latest FLiRT FLuQE with ACE2 antibodies provides a considerable challenge that is explored this study. We combined AlphaFold2-based atomistic predictions structures conformational ensembles spike complexes host dominant JN.1, KP.1, KP.2 KP.3 examine mechanisms underlying role balancing antibody evasion. Using ensemble-based mutational scanning protein residues computations affinities, we identified energy characterized basis epistatic couplings between results suggested existence interactions sites at L455, F456, Q493 positions protect restore ACE2-binding affinity while conferring beneficial escape. To escape mechanisms, performed structure-based profiling several classes displayed impaired neutralization against BA.2.86, KP.3. confirmed experimental data harboring L455S F456L mutations can significantly impair neutralizing activity class 1 monoclonal antibodies, effects mediated by facilitate subsequent convergence Q493E changes rescue binding. Structural energetic analysis provided rationale showing BD55-5840 BD55-5514 bind different epitopes retain efficacy all examined support notion may favor emergence lineages combinations involving mediators control balance high

Language: Английский

Citations

11
Spatiotemporal dynamics and epidemiological impact of SARS-CoV-2 XBB lineage dissemination in Brazil in 2023 DOI Creative Commons
Ighor Arantes, Marcelo Ferreira da Costa Gomes, Kimihito Ito

et al.

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(3)

Published: Feb. 5, 2024

ABSTRACT The SARS-CoV-2 XBB is a group of highly immune-evasive lineages the Omicron variant concern that emerged by recombining BA.2-descendent and spread worldwide during 2023. In this study, we combine genomic data ( n = 11,065 sequences) with epidemiological severe acute respiratory infection (SARI) cases collected in Brazil between October 2022 July 2023 to reconstruct space-time dynamics epidemiologic impact dissemination country. Our analyses revealed introduction local emergence carrying convergent mutations within Spike protein, especially F486P, F456L, L455F, propelled XBB* Brazil. average relative instantaneous reproduction numbers + F486P F456L L455F were estimated be 1.24, 1.33, 1.48 higher than other co-circulating (mainly BQ.1*/BE*), respectively. Despite such growth advantage, these had reduced on Brazil’s scenario concerning previous subvariants. peak number SARI from wave was approximately 90%, 80%, 70% lower observed BA.1*, BA.5*, BQ.1* waves, These findings multiple progressively increasing yet relatively limited throughout stand out for their heightened transmissibility, warranting close monitoring months ahead. IMPORTANCE one most affected countries pandemic, more 700,000 deaths mid-2023. This study reconstructs virus country first half 2023, period characterized descendants XBB.1, recombinant BA.2 evolved late 2022. analysis supports marked continuous indigenous bearing similar key sites process followed increments without repercussions incidence cases. Thus, results suggest influenced an intricate interplay factors extend beyond virus's transmissibility alone. also underlines need surveillance allows its ever-shifting composition.

Language: Английский

Citations

6
Ensemble-Based Mutational Profiling and Network Analysis of the SARS-CoV-2 Spike Omicron XBB Lineages for Interactions with the ACE2 Receptor and Antibodies: Cooperation of Binding Hotspots in Mediating Epistatic Couplings Underlies Binding Mechanism and Immune Escape DOI Open Access
Nishank Raisinghani, Mohammed Alshahrani,

Grace Gupta

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4281 - 4281

Published: April 12, 2024

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with host cell receptor ACE2 and panel diverse class one antibodies. The central objective investigation was to examine molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing antibody evasion variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, XBB.1.5 + L455F/F456L. By combining evolutionary analysis, dynamics simulations, ensemble-based mutational scanning protein residues in complexes ACE2, identified structural stability affinity are consistent results biochemical studies. agreement deep experiments, our quantitative analysis correctly reproduced strong variant-specific effects BA.2 variants. It shown Y453W F456L mutations can enhance when coupled Q493 while these become destabilized R493 position variant. provided rationale mechanism variants, showing role Q493/R493 hotspot modulating between sites L455F lineages. receptors antibodies provide experimental evidence interactions physically proximal Y501, R498, Q493, L455F, determine binding, F486P instrumental mediating broad resistance. supports which impact on is mediated through small group universal hotspots, effect immune could be more variant-dependent modulated by conformationally adaptable regions.

Language: Английский

Citations

6
Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB subvariants DOI Creative Commons

Hisano Yajima,

Tomo Nomai, Kaho Okumura

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(10)

Published: Sept. 16, 2024

ABSTRACT Due to the incessant emergence of various SARS-CoV-2 variants with enhanced fitness in human population, controlling COVID-19 pandemic has been challenging. Understanding how virus enhances its during a could offer valuable insights for more effective control viral epidemics. In this manuscript, we review evolution from early 2022 end 2023—from Omicron BA.2 XBB descendants. Focusing on period, provide concrete examples that increased by enhancing several functions spike (S) protein, including binding affinity ACE2 receptor and ability evade humoral immunity. Furthermore, explore specific mutations modify these S protein through structural alterations. This provides evolutionary, molecular, into repeatedly caused epidemic surges pandemic.

Language: Английский

Citations

4
Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1 DOI Creative Commons

Hisano Yajima,

Yuki Anraku,

Yu Kaku

et al.

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

Published: Oct. 7, 2024

Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts up-conformation. However, whether also interacts with RBD down-conformation facilitate conformational shift RBD-up remains unclear. Herein, we present structures of BA.2.86 JN.1 proteins bound ACE2. Notably, successfully observed ACE2-bound down-RBD, indicating an intermediate structure before conformation. wider mobile angle RBDs up-state provides space interact facilitating transition state. K356T, but not N354-linked glycan, contributes both infectivity neutralizing-antibody evasion BA.2.86. These structural insights spike-protein dynamics would help understand mechanisms underlying infection neutralization.

Language: Английский

Citations

4
A SARS‐CoV‐2 EG.5 mRNA vaccine induces a broad‐spectrum immune response in mice DOI Creative Commons
Hongyu Wang,

Qinhua Peng,

Xinxian Dai

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract The emerging of emergent SARS‐CoV‐2 subvariants has reduced the protective efficacy COVID‐19 vaccines. Therefore, novel vaccines targeting these variants are needed. We designed and prepared CoV072, an mRNA‐based vaccine against Omicron (EG.5) other that encodes EG.5 spike protein. Six‐week‐old female BALB/C mice were used to assess humoral cellular immune responses cross‐reactive neutralizing activity various subvariants. Meanwhile different immunization strategies doses performed detect immunogenicity this mRNA vaccine. Our results show two 5 µg CoV072 or a single dose 15 both induced broad‐spectrum cross‐protection ability in mice. Compared with COV072 exhibited higher levels pseudovirus antibody (PNAb) IgG multiple variants. Moreover, (NAb) live XBB also induced. Th1‐biased response was all vaccination groups. antigen design strategy study have reference significance for research next generation

Language: Английский

Citations

0
A shark-derived broadly neutralizing nanobody targeting a highly conserved epitope on the S2 domain of sarbecoviruses DOI Creative Commons
Bo Feng, Cuiyun Li, Zhaoyong Zhang

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 15, 2025

The continuously evolving Omicron subvariants has diminished the effectiveness of almost all RBD-targeted antibodies in neutralizing these subvariants. development broad-spectrum is desired for addressing both current and future variants. Here, we identified a shark-derived nanobody, 79C11, that can neutralize tested so far, including BA.1 to JN.1 KP.2, exhibits comparable potency against SARS-CoV-1 pangolin coronavirus. Intranasal instillation 79C11 effectively prevent infection subvariant XBB vivo. designs multivalent forms further enhance binding activity. Epitope mapping structure simulation reveal this nanobody binds highly conserved HR1 region S2 domain spikes from sarbecoviruses, suggesting universal vaccine may be designed target eliciting broadly antibody response. This also developed as an intranasally administered prophylactic agent preventing likely SARS-CoV-2 variants, well other animal derived sarbecoviruses infect humans.

Language: Английский

Citations

0
Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern DOI Creative Commons
Ankita Saha, Sounak Ghosh Roy, Richa Dwivedi

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 424 - 424

Published: April 17, 2025

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating severity clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have developed to this effect, including BioNTech-Pfizer Moderna’s mRNA vaccines, as well adenovirus vector-based such Oxford–AstraZeneca. However, emergence new variants subvariants SARS-CoV-2, characterized by enhanced transmissibility immune evasion, poses significant challenges efficacy current vaccination strategies. In review, we aim comprehensively outline landscape emerging concern (VOCs) sub-lineages that recently surfaced post-pandemic years. We assess effectiveness existing their booster doses, against these subvariants, BA.2-derived sub-lineages, XBB BA.2.86 (Pirola). Furthermore, discuss latest advancements vaccine technology, multivalent pan-coronavirus approaches, along development several next-generation coronavirus exosome-based, virus-like particle (VLP), mucosal, nanomaterial-based vaccines. Finally, highlight key critical areas for future research address evolving threat develop strategies combating viral threats, thereby improving preparedness pandemics.

Language: Английский

Citations

0
Exploring the pathogenic and transmission characteristics of JN.1 in golden hamsters based on different attack methods DOI
Ruixue Liu, Fang Song, Li Sun

et al.

Virology, Journal Year: 2025, Volume and Issue: 608, P. 110548 - 110548

Published: April 17, 2025

Language: Английский

Citations

0