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

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 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.

Язык: Английский

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

и другие.

Biomolecules, Год журнала: 2025, Номер 15(2), С. 249 - 249

Опубликована: Фев. 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.

Язык: Английский

Процитировано

0
mRNA-1273 vaccines adapted to JN.1 or KP.2 elicit cross-neutralizing responses against the JN.1 sublineages of SARS-CoV-2 in mice DOI Creative Commons
Diana Lee, Arshan Nasir, Sayda M. Elbashir

и другие.

Vaccine, Год журнала: 2025, Номер 54, С. 126961 - 126961

Опубликована: Март 7, 2025

The continued diversification of SARS-CoV-2 omicron lineage has given rise to the JN.1 variant and descendant strains (KP.2, KP.3, XEC) that have prolonged infection wave. KP.2 show decreased susceptibility neutralization sera in recipients XBB.1.5 vaccine boosters, supporting recent authorization JN.1- KP.2-matched mRNA vaccines United States, Europe, other regions. We evaluated immunogenicity two updated monovalent variant-containing formulations mRNA-1273 encoding spike protein subvariants (mRNA-1273.167) (mRNA-1273.712) as compared with (mRNA-1273.815). were administered either a two-dose primary series naive mice or booster (third) dose previously immunized (ancestral strain). neutralizing antibody response elicited by these against (KP.3 LA.2) recombinant strain (XEC), which achieved dominance States during late 2024, was evaluated. Primary immunization robust titers matched effectively cross-neutralized LA.2, XEC, but not antigenically distant XBB.1.5. Similarly, increased corresponding JN.1-related subvariants, These data suggest are similar relatively few differences between KP.2/JN.1-related subvariants. Our results demonstrate potency KP.2-containing variants their utility cross-neutralizing XEC. Taken together, licensed likely continue protect emerging further evolves.

Язык: Английский

Процитировано

0
SARS-CoV-2 serotyping based on spike antigenicity and its implications for host immune evasion DOI

Wenjing Ruan,

Pengyue Gao, Xiao Qu

и другие.

EBioMedicine, Год журнала: 2025, Номер 114, С. 105634 - 105634

Опубликована: Март 12, 2025

Язык: Английский

Процитировано

0
Entry Efficiency, Protease Dependence, and Antibody-Mediated Neutralization of SARS-CoV-2 Sublineages KP.3.1.1 and XEC DOI Creative Commons
Prerna Arora,

Amy Kempf,

Inga Nehlmeier

и другие.

Vaccines, Год журнала: 2025, Номер 13(4), С. 385 - 385

Опубликована: Апрель 3, 2025

Background: The SARS-CoV-2 variants KP.3.1.1 and XEC currently dominate the COVID-19 epidemic. However, their cell tropism, proteolytic processing, susceptibility to neutralization by monoclonal antibodies remain incompletely characterized. Methods: We employed pseudotyped viruses assess entry efficiency of in various lines, dependence on TMPRSS2 for lung entry, ability use ACE2 infection. Additionally, we evaluated BD55-4637 BD55-5514. Results: entered lines with similar as parental JN.1 lineage utilized Calu-3 entry. Unlike JN.1, failed efficiently murine Both were effectively neutralized BD55-5514, suggesting therapeutic potential. Conclusions: Our findings demonstrate that KP.3.1.1, XEC, like predecessor BA.2.86, rely sensitive certain neutralizing antibodies. these differ utilize species orthologs

Язык: Английский

Процитировано

0
Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC DOI Creative Commons
Qian Wang, Yicheng Guo, Ian A. Mellis

и другие.

Cell Reports, Год журнала: 2025, Номер 44(4), С. 115543 - 115543

Опубликована: Апрель 1, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread, it remains critical understand the functional consequences of mutations in dominant viral variants. The recombinant JN.1 subvariant XEC recently replaced KP.3.1.1 become most prevalent worldwide. Here, we measure vitro neutralization by human sera, monoclonal antibodies, soluble ACE2 (hACE2) receptor relative parental subvariants KP.3 JN.1. are slightly more resistant (1.3- 1.6-fold) than serum antigenically similar. Both also demonstrate greater resistance select antibodies hACE2, all which target top spike. Our findings suggest that upward motion receptor-binding domain spike may be partially hindered N-terminal XEC, allowing these better evade up position have a growth advantage.

Язык: Английский

Процитировано

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 Open Access
Mohammed Alshahrani, Victoria N. Parikh, Brian Foley

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 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.

Язык: Английский

Процитировано

0