AlphaFold2 Predictions of Conformational Ensembles and Atomistic Simulations of the SARS-CoV-2 Spike XBB Lineages Reveal Epistatic Couplings between Convergent Mutational Hotspots that Control ACE2 Affinity DOI
Nishank Raisinghani, Mohammed Alshahrani,

Grace Gupta

et al.

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(19), P. 4696 - 4715

Published: May 2, 2024

In this study, we combined AlphaFold-based atomistic structural modeling, microsecond molecular simulations, mutational profiling, and network analysis to characterize binding mechanisms of the SARS-CoV-2 spike protein with host receptor ACE2 for a series Omicron XBB variants including XBB.1.5, XBB.1.5+L455F, XBB.1.5+F456L, XBB.1.5+L455F+F456L. dynamic modeling Spike lineages can accurately predict experimental structures conformational ensembles complexes ACE2. Microsecond dynamics simulations identified important differences in landscapes equilibrium variants, suggesting that combining AlphaFold predictions multiple conformations provide complementary approach characterization functional states mechanisms. Using ensemble-based profiling residues physics-based rigorous calculations affinities, energy hotspots characterized basis underlying epistatic couplings between convergent hotspots. Consistent experiments, results revealed mediating role Q493 hotspot synchronization L455F F456L mutations, providing quantitative insight into energetic determinants lineages. We also proposed network-based perturbation allosteric communications uncovered relationships centers long-range communication couplings. The study support mechanism which may be determined by effects evolutionary control binding.

Language: Английский

Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike DOI
Qian Wang, Yicheng Guo, Liyuan Liu

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7992), P. 639 - 644

Published: Oct. 23, 2023

Language: Английский

Citations

156
Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion DOI Creative Commons
Delphine Planas, Isabelle Staropoli, Vincent Michel

et al.

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

Published: March 13, 2024

Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicate IGROV-1 no longer Vero E6 are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhances NAb against both BA.2.86 displays affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Language: Английский

Citations

128
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1 DOI Creative Commons
Qian Wang, Yicheng Guo, Anthony Bowen

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(3), P. 315 - 321.e3

Published: Feb. 19, 2024

COVID-19 vaccines have recently been updated to specifically encode or contain the spike protein of SARS-CoV-2 XBB.1.5 subvariant, but their immunogenicity in humans has yet be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report administration an monovalent mRNA vaccine booster (XBB.1.5 MV) previously uninfected individuals boosted serum virus-neutralizing antibodies significantly not only (27.0-fold increase) EG.5.1 (27.6-fold also key emerging such as HV.1, HK.3, JD.1.1, JN.1 (13.3- 27.4-fold increase). Individuals infected by Omicron subvariant had highest overall neutralizing titers (ID

Language: Английский

Citations

111
Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants DOI Creative Commons
Panke Qu, Kai Xu, Julia N. Faraone

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 585 - 595.e6

Published: Jan. 8, 2024

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose-vaccinated bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, monoclonal antibody (mAb) S309. We assessed biology spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially different conformational stability spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Language: Английский

Citations

105
Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants DOI
Panke Qu, Kai Xu, Julia N. Faraone

et al.

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

Published: Sept. 12, 2023

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose vaccinated bivalent healthcare workers, XBB.1.5-wave infected first responders, monoclonal antibody (mAb) S309. We assessed biology Spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially differences conformational stability Spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Language: Английский

Citations

46
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants DOI Creative Commons
Qian Wang, Yicheng Guo, Anthony Bowen

et al.

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

Published: Nov. 27, 2023

Summary COVID-19 vaccines have recently been updated with the spike protein of SARS-CoV-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report administration an monovalent mRNA vaccine (XBB.1.5 MV) uninfected individuals boosted serum virus-neutralization antibodies significantly not only (27.0-fold) currently dominant EG.5.1 (27.6-fold) also key like HV.1, HK.3, JD.1.1, JN.1 (13.3-to-27.4-fold). In previously infected by Omicron subvariant, neutralizing titers were highest levels (1,504-to-22,978) all viral variants tested. While immunological imprinting was still evident vaccines, it nearly as severe authorized bivalent BA.5 vaccine. Our findings strongly support official recommendation widely apply further protect public.

Language: Английский

Citations

43
A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2 DOI Creative Commons

Zijing Jia,

Kang Wang,

Minxiang Xie

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(12), P. 930 - 937

Published: May 25, 2024

Language: Английский

Citations

36
Evolution of the SARS-CoV-2 Omicron Variants: Genetic Impact on Viral Fitness DOI Creative Commons
Wenhao Liu, Zehong Huang, Jin Xiao

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 184 - 184

Published: Jan. 25, 2024

Over the last three years, pandemic of COVID-19 has had a significant impact on people’s lives and global economy. The incessant emergence variant strains compounded challenges associated with management COVID-19. As predominant from late 2021 to present, Omicron its sublineages, through continuous evolution, have demonstrated iterative viral fitness. comprehensive elucidation biological implications that catalyzed this evolution remains incomplete. In accordance extant research evidence, we provide review subvariants Omicron, delineating alterations in immune evasion, cellular infectivity, cross-species transmission potential. This seeks clarify underpinnings biology within SARS-CoV-2, thereby providing foundation for strategic considerations post-pandemic era

Language: Английский

Citations

23
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
Enabling the immune escaped etesevimab fully-armed against SARS-CoV-2 Omicron subvariants including KP.2 DOI Creative Commons
Chao Su,

Juanhua He,

Yufeng Xie

et al.

hLife, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2