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

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

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Key Essentials during the Transition from the Acute Phase of the COVID-19 Pandemic

Published: Aug. 17, 2023

The COVID-19 pandemic has been met with an unprecedented response from the scientific community leading to development, study, and authorization of vaccines antivirals, ultimately reducing impact SARS-CoV-2 on global public health. However, is far being eradicated, continues evolve, causes substantial health economic burdens. In this paper, we posit essential points its management during transition acute phase pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that future (sub)lineages do not necessarily have be milder. Antivirals remain elements in management. former could benefit further development improvements dosing, while seasonal administration latter simplification increase interest tackle vaccine hesitancy. also ensure accessibility pharmaceuticals low-income countries improve understanding their use context long-term goals Regardless location, primary role awareness education must played by healthcare workers who directly communicate patients serve as models for healthy behaviors.

Language: Английский

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From Emergence to Endemicity: A Comprehensive Review of COVID-19

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 31, 2023

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), later renamed coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China, early December 2019. Initially, the China office of World Health Organization informed numerous cases pneumonia unidentified etiology Hubei Province at end This would subsequently result a global pandemic with millions confirmed COVID-19 and deaths reported to WHO. We have analyzed most data published since beginning compile this comprehensive review SARS-CoV-2. looked core ideas, such as etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, vaccines. also included long-term effects myths associated some therapeutics COVID-19. study presents assessment SARS-CoV-2 virology, vaccines, medicines, significant variants during course pandemic. Our article is intended provide medical practitioners better understanding fundamental sciences, treatment, prevention As May 2023, paper contains recent made accessible.

Language: Английский

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Flu-COVID combo recombinant protein vaccines elicited protective immune responses against both influenza and SARS-CoV-2 viruses infection

Vaccine, Journal Year: 2024, Volume and Issue: 42(5), P. 1184 - 1192

Published: Jan. 30, 2024

Language: Английский

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Editorial: Global Health Concerns as Vaccine-Preventable Infections Including SARS-CoV-2 (JN.1), Influenza, Respiratory Syncytial Virus (RSV), and Measles Continue to Rise

Medical Science Monitor, Journal Year: 2024, Volume and Issue: 30

Published: Feb. 1, 2024

In December 2023, the US Centers for Disease Control and Prevention (CDC) published updated 2024 Advisory Committee on Immunization Practices (ACIP) Adult Schedule, which is available online access by public healthcare professionals. These new guidelines come at a time when incidence of vaccine-preventable viral infections from SARS-CoV-2 (JN.1), respiratory syncytial virus (RSV), influenza, measles are increasing in adults children due to vaccine hesitancy, or non-compliance. This editorial aims highlight ongoing global health concerns consequences reports infections, including RSV, measles, understand causes introduce some measures that could improve uptake.

Language: Английский

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A SARS‐CoV‐2 EG.5 mRNA vaccine induces a broad‐spectrum immune response in mice

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

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Genomic and epidemiological surveillance of SARS-CoV-2 variants during the pre-mass vaccination period in Botucatu, Brazil

Virus Genes, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Language: Английский

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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

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

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Genomic Epidemiology of the Main SARS‐CoV‐2 Variants Circulating in Italy During the Omicron Era

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT Since early 2022 the Omicron variant has rapidly spread worldwide, becoming dominant to date. The study aimed investigate clinical and epidemiological characteristics of COVID‐19 patients reconstruct genomic epidemiology main SARS‐CoV‐2 sublineages in Italy 2022. A total 8970 samples were studied, phylogenetic analyses focused on BA.1, BA.2, BA.5 subvariants. More than half subjects received three doses vaccine experienced a reinfection. significant larger proportion unvaccinated presented reinfection compared with vaccinated. Clusters tMRCA between September–November 2021 (BA.1), November 2021–January (BA.2), October 2021–May (BA.5). R e values showed highest level September–October, January–February 2022, May for BA.2 BA.5, respectively. Limited number studied sequences are included clusters. rate exceeded its evolutionary rate. No single sublineage had sufficient time differentiate into large clusters, but only small fragmented groups sharing same recent ancestor. These dissect dynamics over period great changes epidemic.

Language: Английский

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Conformational and Stability Analysis of SARS-CoV-2 Spike Protein Variants by Molecular Simulation

Pathogens, Journal Year: 2025, Volume and Issue: 14(3), P. 274 - 274

Published: March 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.

Language: Английский

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