Semi-Covariance Coefficient Analysis of Spike Proteins from SARS-CoV-2 and Its Variants Omicron, BA.5, EG.5, and JN.1 for Viral Infectivity, Virulence and Immune Escape DOI Creative Commons
Botao Zhu, Huancheng Lin, Jun Steed Huang

и другие.

Viruses, Год журнала: 2024, Номер 16(8), С. 1192 - 1192

Опубликована: Июль 25, 2024

Semi-covariance has attracted significant attention in recent years and is increasingly employed to elucidate statistical phenomena exhibiting fluctuations, such as the similarity or difference charge patterns of spike proteins among coronaviruses. In this study, by examining values above below average/mean based on positive negative amino acid residues SARS-CoV-2 its current circulating variants, proposed methods offer profound insights into nonlinear evolving trends those viral proteins. Our study indicates that span value can predict infectivity virus density estimate virulence virus, both predicated appear be associated with capability immune escape. This semi-covariance coefficient analysis may used not only infectivity, escape for coronaviruses but also analyze functionality other improves our understanding trend evolution terms escape, which remains further validated more future studies data.

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

2
Large‐Scale FMO‐MP2 Calculations of the Spike Protein Droplet Model DOI Creative Commons
Hideo Doi, Tatsuya Nakano,

Kota Sakakura

и другие.

Journal of Computational Chemistry, Год журнала: 2025, Номер 46(4)

Опубликована: Фев. 2, 2025

ABSTRACT The spike protein of SARS‐CoV‐2 is a challenging target for theoretical approaches. Here we report benchmark calculation the droplet model by fragment molecular orbital (FMO) at second‐order Møller‐Plesset perturbation (MP2) level on supercomputer Fugaku. One hundred structure samples from dynamics (MD) simulations were used both closed and open forms this (PDB IDs 6XLU 6XM0 respectively). number total fragments about 20,000, job time per was 2 h 8 racks

Язык: Английский

Процитировано

1
Molecular Determinants for the Binding of the Highly Infectious SARS-CoV-2 Omicron (BA.1) Variant to the Human ACE2 Receptor DOI Creative Commons

Majed S. Aljohani,

Pawan Bhatta,

Xiche Hu

и другие.

Physchem, Год журнала: 2025, Номер 5(1), С. 8 - 8

Опубликована: Фев. 20, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continually undergoes mutation, leading to variants with altered pathogenicity and transmissibility. The Omicron variant (B.1.1.529), first identified in South Africa 2021, has become dominant strain worldwide. It harbors approximately 50 mutations compared original strain, 15 located receptor-binding domain (RBD) spike protein that facilitates viral entry via binding human angiotensin-converting enzyme (ACE2) receptor. How do these mutated residues modulate intermolecular interactions affinity between RBD ACE2? This is a question great theoretical importance practical implication. In this study, we employed quantum chemical calculations at B2PLYP-D3/def2-TZVP level theory investigate molecular determinants governing Omicron’s ACE2 interaction. Comparative analysis wild-type RBD–ACE2 interfaces revealed including S477N, Q493R, Q498R, N501Y enhance through formation bifurcated hydrogen bonds, π–π stacking, cation–π interactions. These favorable counterbalance such destabilizing as K417N, G446S, G496S, Y505H, which disrupt salt bridges bonds. Additionally, allosteric effects improve contributions non-mutated (notably A475, Y453, F486) structural realignment novel bonding S19, an overall increase electrostatic π-system interaction energy. conclusion, our findings provide mechanistic basis for increased infectivity offer valuable insights development targeted antiviral therapies. Moreover, from methodological perspective, directly calculated mutation-induced energy changes residue using advanced methods rather than relying on indirect decomposition schemes typical dynamics-based free analyses. strong correlation differences experimental deep mutational scanning (DMS) data underscores robustness framework predicting affinity. demonstrates potential predictive tools studying protein–protein guiding rational therapeutic design.

Язык: Английский

Процитировано

1
Biophysics of SARS-CoV-2 spike protein’s receptor-binding domain interaction with ACE2 and neutralizing antibodies: from computation to functional insights DOI
Fernando Luís Barroso da Silva,

Karen Paco,

Aatto Laaksonen

и другие.

Biophysical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Язык: Английский

Процитировано

1
Conformational and Stability Analysis of SARS-CoV-2 Spike Protein Variants by Molecular Simulation DOI Creative Commons
Gustavo E. Olivos-Ramírez, Luis Fernando Cofas‐Vargas, Tobias Madl

и другие.

Pathogens, Год журнала: 2025, Номер 14(3), С. 274 - 274

Опубликована: Март 12, 2025

We performed a comprehensive structural analysis of the conformational space several spike (S) protein variants using molecular dynamics (MD) simulations. Specifically, we examined four well-known (Delta, BA.1, XBB.1.5, and JN.1) alongside wild-type (WT) form SARS-CoV-2. The states each variant were characterized by analyzing their distributions within selected collective variables (CVs), such as inter-domain distances between receptor-binding domain (RBD) N-terminal (NTD). Our primary focus was to identify relevant potential transitions determine set native contacts (NCs) that stabilize these conformations. results reveal genetically more distant variants, JN.1, tend adopt compact compared WT. Additionally, exhibit novel NC profiles, an increased number specific distributed among ionic, polar, nonpolar residues. further analyzed impact mutations, including T478K, N500Y, Y504H. These mutations not only enhance interactions with human host receptor but also alter inter-chain stability introducing additional NCs Consequently, may influence accessibility certain regions neutralizing antibodies. Overall, findings contribute deeper understanding functional variations S variants.

Язык: Английский

Процитировано

0
Increased preference for lysine over arginine in spike proteins of SARS-CoV-2 BA.2.86 variant and its daughter lineages DOI Creative Commons
Anže Božič, Rudolf Podgornik

PLoS ONE, Год журнала: 2025, Номер 20(4), С. e0320891 - e0320891

Опубликована: Апрель 7, 2025

The COVID-19 pandemic offered an unprecedented glimpse into the evolution of its causative virus, SARS-CoV-2. It has been estimated that since outbreak in late 2019, virus explored all possible alternatives terms missense mutations for sites polypeptide chain. Spike protein exhibits largest sequence variation particular, with many individual impacting target recognition, cellular entry, and endosomal escape virus. Moreover, recent studies unveiled a significant increase total charge on spike during initial period pandemic. While this trend recently come to halt, we perform sequence-based analysis 2665 SARS-CoV-2 variants which shows ionizable amino acids continue occur newly emerging variants, notable differences between lineages from different clades. What is more, show within can acquire positive charge, prominent preference lysine residues over arginine residues. This lysine-to-arginine ratio increased at several points evolution, most BA.2.86 sublineages, including dominant JN.1, KP.3, XEC variants. consequence structural regions now among highest viral species Coronaviridae family. impact high proteins daughter fitness remains unclear; discuss potential mechanisms could play role serve as starting point further studies.

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
Semi-Covariance Coefficient Analysis of Spike Proteins from SARS-CoV-2 and Its Variants Omicron, BA.5, EG.5, and JN.1 for Viral Infectivity, Virulence and Immune Escape DOI Creative Commons
Botao Zhu, Huancheng Lin, Jun Steed Huang

и другие.

Viruses, Год журнала: 2024, Номер 16(8), С. 1192 - 1192

Опубликована: Июль 25, 2024

Semi-covariance has attracted significant attention in recent years and is increasingly employed to elucidate statistical phenomena exhibiting fluctuations, such as the similarity or difference charge patterns of spike proteins among coronaviruses. In this study, by examining values above below average/mean based on positive negative amino acid residues SARS-CoV-2 its current circulating variants, proposed methods offer profound insights into nonlinear evolving trends those viral proteins. Our study indicates that span value can predict infectivity virus density estimate virulence virus, both predicated appear be associated with capability immune escape. This semi-covariance coefficient analysis may used not only infectivity, escape for coronaviruses but also analyze functionality other improves our understanding trend evolution terms escape, which remains further validated more future studies data.

Язык: Английский

Процитировано

0