Prevalence of symptoms, comorbidities, and reinfections in individuals infected with Wild-Type SARS-CoV-2, Delta, or Omicron variants: a comparative study in western Mexico

Frontiers in Public Health, Год журнала: 2023, Номер 11

Опубликована: Апрель 27, 2023

Introduction The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been classified into interest (VOIs) or concern (VOCs) to prioritize global monitoring and research on with potential risks public health. SARS-CoV-2 high-rate mutation can directly impact the clinical disease progression, epidemiological behavior, immune evasion, vaccine efficacy, transmission rates. Therefore, surveillance is crucial for controlling COVID-19 pandemic. In present study, we aimed describe prevalence wild-type (WT) Delta Omicron in Jalisco State, Mexico, from 2021 2022, evaluate possible association these manifestations COVID-19. Methods Four thousand ninety-eight patients diagnosed by real-time PCR (COVIFLU, Genes2Life, Mexico) nasopharyngeal samples January 2022 were included. Variant identification was performed RT-qPCR Master Mut Kit (Genes2Life, Mexico). A study population follow-up identify who had experienced reinfection after being vaccinated. Results Discussion Samples grouped according identified mutations: 46.3% Omicron, 27.9% Delta, 25.8% WT. proportions dry cough, fatigue, headache, muscle pain, conjunctivitis, fast breathing, diarrhea, anosmia, dysgeusia significantly different among abovementioned groups ( p < 0.001). Anosmia mainly found WT-infected patients, while rhinorrhea sore throat more prevalent infected variant. For follow-up, 836 answered, which 85 cases (9.6%); VOC that caused all reported cases. this demonstrate variant biggest outbreak during pandemic late December mid-February but a less form than one demonstrated co-analysis mutations outcomes health strategy infer could increase severity even be an indicator long-term sequelae

Язык: Английский

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Ensemble-Based Mutational Profiling and Network Analysis of the SARS-CoV-2 Spike Omicron XBB Lineages for Interactions with the ACE2 Receptor and Antibodies: Cooperation of Binding Hotspots in Mediating Epistatic Couplings Underlies Binding Mechanism and Immune Escape

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4281 - 4281

Опубликована: Апрель 12, 2024

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with host cell receptor ACE2 and panel diverse class one antibodies. The central objective investigation was to examine molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing antibody evasion variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, XBB.1.5 + L455F/F456L. By combining evolutionary analysis, dynamics simulations, ensemble-based mutational scanning protein residues in complexes ACE2, identified structural stability affinity are consistent results biochemical studies. agreement deep experiments, our quantitative analysis correctly reproduced strong variant-specific effects BA.2 variants. It shown Y453W F456L mutations can enhance when coupled Q493 while these become destabilized R493 position variant. provided rationale mechanism variants, showing role Q493/R493 hotspot modulating between sites L455F lineages. receptors antibodies provide experimental evidence interactions physically proximal Y501, R498, Q493, L455F, determine binding, F486P instrumental mediating broad resistance. supports which impact on is mediated through small group universal hotspots, effect immune could be more variant-dependent modulated by conformationally adaptable regions.

Язык: Английский

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Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 7, 2024

Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts up-conformation. However, whether also interacts with RBD down-conformation facilitate conformational shift RBD-up remains unclear. Herein, we present structures of BA.2.86 JN.1 proteins bound ACE2. Notably, successfully observed ACE2-bound down-RBD, indicating an intermediate structure before conformation. wider mobile angle RBDs up-state provides space interact facilitating transition state. K356T, but not N354-linked glycan, contributes both infectivity neutralizing-antibody evasion BA.2.86. These structural insights spike-protein dynamics would help understand mechanisms underlying infection neutralization.

Язык: Английский

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Molecular insights and optimization strategies for the competitive binding of engineered ACE2 proteins: a multiple replica molecular dynamics study

Physical Chemistry Chemical Physics, Год журнала: 2023, Номер 25(41), С. 28479 - 28496

Опубликована: Янв. 1, 2023

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally, and rapid viral evolution the emergence of new variants pose challenges control. During infection, spike protein SARS-CoV-2 interacts with human ACE2 via its receptor binding domain (RBD), it is known that engineered forms can compete wild-type (WT) for inhibit infection. Here, we conducted multiple replica molecular dynamics (MRMD) simulations study mechanisms 3N39 3N94 provide directions optimization. Our findings reveal notably more efficacious in systems show weaker WT (i.e., BA.1 RBD), but also faces immune escape as virus evolves. Moreover, modifying residue types near interface, alters electrostatic potential distribution reconfigures hydrogen bonding network, which results modified RBD. However, this structural rearrangement does not occur all RBD variants. In addition, identified potentially engineerable beneficial residues detrimental both Functional conservation thus enable optimization these improve competitiveness ACE2, therefore provides additional prevention. Finally, conclude have implications understanding responsible help us develop proteins superior performance.

Язык: Английский

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SARS‐CoV‐2 Omicron (BA.4, BA.5) variant: Lessons learned from a new variant during the COVID‐19 pandemic

Health Science Reports, Год журнала: 2024, Номер 7(2)

Опубликована: Фев. 1, 2024

Abstract Background and Aim In late 2021, the world faced rapid spread of SARS‐CoV‐2 Omicron variant, which quickly became variant concern. April 2022, two new lineages (BA.4/BA.5) emerged from Africa, where they caused fifth wave infection. Method We searched PubMed, Google Scholar, Scopus online databases up to December 2023 for founding relevant studies. Results BA.4 BA.5 subgroups, with changes in spike protein, have a greater ability escape immune system, was possible help L452R F486V mutations. Epidemiologically, these evolving subtypes show similarities seasonal influenza but higher mortality rates. The symptoms subgroups are different previous types form upper respiratory symptoms. Antiviral treatments, use antibodies such as bebtelovimab, development vaccines promising. Conclusion Consequently, we must continue be vigilant our joint surveillance efforts against COVID‐19 diagnosis treatment.

Язык: Английский

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A slow but steady nanoLuc: R162A mutation results in a decreased, but stable, nanoLuc activity

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 269, С. 131864 - 131864

Опубликована: Апрель 29, 2024

NanoLuc (NLuc) luciferase has found extensive application in designing a range of biological assays, including gene expression analysis, protein-protein interaction, and protein conformational changes due to its enhanced brightness small size. However, questions related mechanism interaction with the substrate, furimazine, as well bioluminescence activity remain elusive. Here, we combined molecular dynamics (MD) simulation mutational analysis show that R162A mutation results decreased but stable NLuc living cells vitro. Specifically, performed multiple, all-atom, explicit solvent MD simulations apo furimazine-docked (holo) structures revealing differential absence presence ligand. Further, trajectories for hydrogen bonds (H-bonds) formed between furimazine revealed substantial H-bond R162 Q32 residues. Mutation two residues R162A, not Q32A, mutant live cell vitro assays using lysates prepared from expressing proteins substrate. In addition highlighting role residue activity, believe will find wide requiring extended monitoring activity. Bioluminescence been extensively utilized developing variety biomedical assays. this regard, engineering brighter bioluminescent proteins, i.e. luciferases, played significant role. This is acutely exemplified by luciferase, which size displays much thermal stability compared previously available luciferases. While desirable multitude it would also be useful develop variants display prolonged specifically relevant require periods, such case biosensors designed slow enzymatic or cellular signaling reactions, without necessitating multiple rounds substrate any specialized reagents result increased assay costs. current manuscript, report possesses albeit lower than wild-type NLuc, envisage wider slower events.

Язык: Английский

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Unraveling the Dynamics of Omicron (BA.1, BA.2, and BA.5) Waves and Emergence of the Deltacron Variant: Genomic Epidemiology of the SARS-CoV-2 Epidemic in Cyprus (Oct 2021–Oct 2022)

Viruses, Год журнала: 2023, Номер 15(9), С. 1933 - 1933

Опубликована: Сен. 15, 2023

Commencing in December 2019 with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three years disease (COVID-19) pandemic have transpired. The virus has consistently demonstrated a tendency for evolutionary adaptation, resulting mutations that impact both immune evasion and transmissibility. This ongoing process led to successive waves infections. study offers comprehensive assessment spanning genetic, phylogenetic, phylodynamic, phylogeographic dimensions, focused on trajectory SARS-CoV-2 epidemic Cyprus. Based dataset comprising 4700 viral genomic sequences obtained from affected individuals between October 2021 2022, our analysis is presented. Over this timeframe, total 167 distinct lineages sublineages emerged, including variants such as Delta Omicron (1, 2, 5). Notably, during fifth wave infections, subvariants 1 gained prominence, followed by ascendancy 5 subsequent sixth wave. Additionally, (December 2021-January 2022), unique set genetic associated variant 1, dubbed "Deltacron", was identified. phenomenon initially evoked skepticism, characterized concerns primarily centered around contamination or coinfection plausible etiological contributors. These hypotheses were predominantly disseminated through unsubstantiated assertions within realms social mass media, lacking concurrent scientific evidence validate their claims. Nevertheless, exhaustive molecular analyses presented occurrences would likely lead frameshift mutation-a aberration conspicuously absent provided sequences. substantiates accuracy initial assertion while refuting potential etiologies. Comparable observations global scale dispelled doubt, eventually leading recognition Delta-Omicron community monitoring World Health Organization (WHO). As investigation delved deeper into intricate dynamics Cyprus, discernible pattern highlighting major role international connections shaping virus's local trajectory. United States Kingdom central conduits governing entry exit Moreover, notable migratory routes included nations Greece, South Korea, France, Germany, Brazil, Spain, Australia, Denmark, Sweden, Italy. empirical findings underscore spread Cyprus markedly influenced influx new, highly transmissible variants, triggering infection. elucidates new infection advent contagious notably an abundance localized spike protein. discovery decisively contradicts hitherto hypothesis seasonal fluctuations epidemiological dynamics. emphasizes importance meticulously examining genetics alongside migration patterns specific region. Past experiences also emphasize substantial viruses SARS-CoV-2, underscoring need sustained vigilance. However, pandemic's continue evolve, balanced approach caution resilience becomes paramount. ethos encourages founded informed prudence self-preservation, guided public health authorities, rather than enduring apprehension. Such empowers societies adapt progress, fostering poised confidence rooted well-founded adaptation.

Язык: Английский

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AlphaFold2-Enabled Atomistic Modeling of Structure, Conformational Ensembles, and Binding Energetics of the SARS-CoV-2 Omicron BA.2.86 Spike Protein with ACE2 Host Receptor and Antibodies: Compensatory Functional Effects of Binding Hotspots in Modulating Mechanisms of Receptor Binding and Immune Escape

Journal of Chemical Information and Modeling, Год журнала: 2024, Номер 64(5), С. 1657 - 1681

Опубликована: Фев. 19, 2024

The latest wave of SARS-CoV-2 Omicron variants displayed a growth advantage and increased viral fitness through convergent evolution functional hotspots that work synchronously to balance requirements for productive receptor binding efficient immune evasion. In this study, we combined AlphaFold2-based structural modeling approaches with atomistic simulations mutational profiling energetics stability prediction comprehensive analysis the structure, dynamics, BA.2.86 spike variant ACE2 host distinct classes antibodies. We adapted several AlphaFold2 predict both structure conformational ensembles protein in complex receptor. results showed AlphaFold2-predicted ensemble can accurately capture main states variant. Complementary predictions, microsecond molecular dynamics reveal details landscape produced equilibrium structures are used perform scanning residues characterize energy hotspots. ensemble-based domain BA.2 complexes revealed group conserved hydrophobic critical variant-specific contributions R403K, F486P, R493Q. To examine evasion properties detail, performed structure-based interfaces antibodies significantly reduced neutralization against basis compensatory effects hotspots, showing lineage may have evolved outcompete other subvariants by improving while preserving affinity via effect R493Q F486P This study demonstrated an integrative approach combining predictions complementary robust enable accurate characterization mechanisms newly emerging variants.

Язык: Английский

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Unraveling the binding mechanisms of SARS-CoV-2 variants through molecular simulations

Heliyon, Год журнала: 2024, Номер 10(5), С. e27193 - e27193

Опубликована: Фев. 29, 2024

The emergence of SARS-CoV-2 variants like Delta (AY.29) and Omicron (EG.5) poses continued challenges for vaccines therapeutics. Mutations in the viral spike protein are key altering infectivity immune evasion. This study uses computational modeling to investigate molecular binding mechanisms between ACE2 host receptor. Using MARTNI force field, coarse-grained dynamics (CGMD) simulations nudged elastic band (NEB) calculations explore spike-ACE2 interactions wild type, variant, variant. reveal has strongest affinity at -128.35 ± 10.91 kcal/mol, followed by type. Key mutations Omicron, Q493R Q498R, optimize electrostatic contacts, enhancing interactions. wild-type highest transition state energy barrier 17.87 while lowest 9.21 kcal/mol. Despite slightly higher dual barriers, Omicron's increased lowers its overall rapidly bind ACE2. These findings provide residue-level insights into mutation effects on infectivity. elucidates underlying kinetics, aiding development therapies targeting emerging strains.

Язык: Английский

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Impact of mutations defining SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 on Spike function and neutralization

iScience, Год журнала: 2023, Номер 26(11), С. 108299 - 108299

Опубликована: Окт. 27, 2023

Additional mutations in the viral Spike protein helped BA.2.12.1 and BA.4/5 SARS-CoV-2 Omicron subvariants to outcompete parental BA.2 subvariant. Here, we determined functional impact of that newly emerged (L452Q, S704L) (Δ69-70, L452R, F486V, R493Q) proteins. Our results show mutation L452Q/R or F486V typically increases R493Q S704L impair Spike-mediated infection. In combination, changes Δ69-70, contribute higher infectiousness fusogenicity Spike. L452R/Q are mainly responsible for reduced sensitivity neutralizing antibodies. However, combined required full infectivity, TMPRSS2 dependency, immune escape Thus, it is specific combination allows increased functionality evasion, which helps explain temporary dominance pathogenicity these subvariants.

Язык: Английский

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