Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies DOI Open Access
Mohammed Alshahrani, Victoria N. Parikh, Brian Foley

et al.

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

Published: Dec. 20, 2024

Abstract The growing body of experimental and computational studies suggested that the cross-neutralization antibody activity against Omicron variants may be driven by balance tradeoff multiple energetic factors interaction contributions evolving escape hotspots involved in antigenic drift convergent evolution. However, dynamic details quantifying contribution these factors, particularly balancing nature specific interactions formed antibodies with epitope residues remain scarcely characterized. In this study, we performed molecular dynamics simulations, ensemble-based deep mutational scanning SARS-CoV-2 spike binding free energy computations for two distinct groups broadly neutralizing : E1 group (BD55-3152, BD55-3546 BD5-5840) F3 (BD55-3372, BD55-4637 BD55-5514). Using approaches, examine determinants which potent can largely evade immune resistance. Our analysis revealed emergence a small number positions correspond to R346 K444 strong van der Waals act synchronously leading large contribution. According our results, Abs effectively exploit hotspot clusters hydrophobic sites critical functions along selective complementary targeting positively charged are important ACE2 binding. Together conserved epitopes, lead expanded neutralization breadth resilience shift associated viral results study demonstrate excellent qualitative agreement between predicted mutations respect latest experiments on average scores. We argue epitopes leverage stability binding, while tend emerge synergistically electrostatic interactions.

Language: Английский

The rising SARS‐CoV‐2 JN.1 variant: evolution, infectivity, immune escape, and response strategies DOI Creative Commons
Yishan Lu, Danyi Ao,

Xuemei He

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 29, 2024

The JN.1 variant of COVID-19 has emerged as the dominant strain worldwide since end 2023. As a subclade BA.2.86 variant, harbors unique combination mutations inherited from lineage, notably featuring novel L455S mutation within its receptor-binding motif. This been linked to increased transmissibility and enhanced immune evasion capabilities. During rise JN.1, evidence resistance various monoclonal antibodies reduced cross-neutralization effects XBB.1.5 vaccine have observed. Although public health threat posed by appears relatively low, concerns persist regarding evolutionary trajectory under pressure. review provides comprehensive overview evolving highlighting need for continuous monitoring investigation new variants that could lead widespread infection. It assesses efficacy current vaccines therapeutics against emerging variants, particularly focusing on immunocompromised populations. Additionally, this summarizes potential advancements clinical treatments COVID-19, offering insights optimize prevention treatment strategies. thoroughly evaluates variant's impact implications future therapeutic development, contributing ongoing efforts mitigate risk virus transmission disease severity.

Language: Английский

Citations

9
SARS-CoV-2 serotyping based on spike antigenicity and its implications for host immune evasion DOI

Wenjing Ruan,

Pengyue Gao, Xiao Qu

et al.

EBioMedicine, Journal Year: 2025, Volume and Issue: 114, P. 105634 - 105634

Published: March 12, 2025

Language: Английский

Citations

1
Recurrent SARS-CoV-2 spike mutations confer growth advantages to select JN.1 sublineages DOI Open Access
Qian Wang, Ian A. Mellis, Anthony Bowen

et al.

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

Published: May 29, 2024

Abstract The recently dominant SARS-CoV-2 Omicron JN.1 has evolved into multiple sublineages, with recurrent spike mutations R346T, F456L, and T572I, some of which exhibit growth advantages, such as KP.2. We investigated these in JN.1, examining their individual combined effects on immune evasion, ACE2 receptor affinity, vitro infectivity. F456L increased resistance to neutralization by human sera, including those after breakthrough infections, RBD class-1 monoclonal antibodies, significantly altering antigenicity. R346T enhanced ACE2-binding without a discernible effect serum neutralization. Individually, T572I modestly infectivity each pseudovirus. Importantly, expanding sublineages KP.2 containing V1104L, showed similar suggesting V1104L does not appreciably affect antibody evasion. Our findings illustrate how certain confer advantages the population could inform design next COVID-19 vaccine booster.

Language: Английский

Citations

6
Investigating the FLiRT Variants of COVID-19: Is it An Emerging Concern? DOI
Durre Aden, Sufian Zaheer

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 262, P. 155542 - 155542

Published: Aug. 13, 2024

Language: Английский

Citations

6
Atomistic Prediction of Structures, Conformational Ensembles and Binding Energetics for the SARS-CoV-2 Spike JN.1, KP.2 and KP.3 Variants Using AlphaFold2 and Molecular Dynamics Simulations: Mutational Profiling and Binding Free Energy Analysis Reveal Epistatic Hotspots of the ACE2 Affinity and Immune Escape DOI
Nishank Raisinghani, Mohammed Alshahrani,

Grace Gupta

et al.

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

Published: July 10, 2024

Abstract 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 spike protein residues computations affinities, we identified energy characterized basis epistatic couplings between results suggested existence interactions sites at L455, F456, Q493 positions enable protect restore 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

5
Safety and Immunogenicity of Omicron Protein Vaccines in mRNA-Vaccinated Adolescents: A Phase 3, Randomised Trial DOI Creative Commons

Chijioke Bennett,

Gordon Chau,

Elizabeth Clayton

et al.

Journal of Infection, Journal Year: 2025, Volume and Issue: unknown, P. 106428 - 106428

Published: Jan. 1, 2025

Language: Английский

Citations

0
Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients DOI
Qian Wu,

Hairuo Wu,

Yabin Hu

et al.

Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106092 - 106092

Published: Jan. 1, 2025

Language: Английский

Citations

0
Neutralizing antibody responses to three XBB protein vaccines in older adults DOI Creative Commons

Guo‐Jian Yang,

Mei Lu, Rui-Rui Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 2, 2025

Language: Английский

Citations

0
Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies DOI Creative Commons
Mohammed Alshahrani,

Vedant Parikh,

Brian Foley

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 249 - 249

Published: Feb. 8, 2025

A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by balance tradeoff between multiple energetic factors interaction contributions evolving escape hotspots involved in antigenic drift convergent evolution. However, dynamic details quantifying contribution these factors, particularly balancing nature specific interactions formed antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning SARS-CoV-2 spike binding free energy computations for two distinct groups broadly neutralizing antibodies: E1 group (BD55-3152, BD55-3546, BD5-5840) F3 (BD55-3372, BD55-4637, BD55-5514). Using approaches, examined determinants which potent can evade immune resistance. Our analysis revealed emergence a small number positions correspond to R346 K444 strong van der Waals act synchronously, leading large contribution. According our results, Abs effectively exploit hotspot clusters hydrophobic sites are critical functions along selective complementary targeting positively charged important ACE2 binding. Together conserved epitopes, lead expand breadth resilience neutralization shifts associated viral The results study demonstrate excellent qualitative agreement predicted mutations respect latest experiments on average scores. We argue epitopes leverage stability binding, while tend emerge synergistically electrostatic interactions.

Language: Английский

Citations

0
Evaluation of sampling methods for genomic surveillance of SARS-CoV-2 variants in aircraft wastewater samples DOI Creative Commons
Opeyemi U. Lawal, Valeria R. Parreira,

Fozia Rizvi

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing threat to global health. Wastewater-based surveillance (WBS) has proven be important tool for tracking the dissemination of SARS-CoV-2 variants concern (VOCs) in community. In Canada, metagenomic analysis aircraft wastewater was adopted at early stage pandemic track importation emerging into country. However, need determine presence sublineages meant that sampling methods utilized were not adequately validated. Here, we compared two different genomic VOCs sewage samples. Methods Eighty-eight composite samples collected over nine weeks using both autosampler and passive torpedo samplers same location. nucleic acid quantified RT-qPCR. RNA extracted sequenced with MiniSeq system tiled-amplicon sequencing approach ARTIC V4.1 primer sets. Raw reads preprocessed mutations, lineages, other sequence metrics from compared. Results The yielded comparable viral load by RT-qPCR, but produced higher genome coverage relative samplers. Omicron lineages identified differed method. BQ.1* BA.5.2*, which predominant clinical time, as dominant sampler, respectively. Additionally, captured diversity abundance VOCs, including (XBB* CH.1* lineages), well more clinically relevant mutations (S:K444T, T22942A, S:R346T) sampler. Overall, the passive concordant results measuring RT-qPCR wastewater. Conclusions Taken together, our suggest underestimation These data can used optimize approaches

Language: Английский

Citations

0