A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

Viruses, Год журнала: 2023, Номер 15(1), С. 167 - 167

Опубликована: Янв. 5, 2023

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all previously emerged variants. numerous mutations in Omicron’s viral genome sub-lineages attribute it a larger amount of fitness, owing to alteration transmission pathophysiology virus. With rapid change structure, sub-variants, namely BA.1, BA.2, BA.3, BA.4, BA.5, dominate community with an ability escape neutralization efficiency induced prior vaccination or infections. Similarly, several recombinant sub-variants Omicron, XBB, XBD, XBF, etc., have emerged, which better understanding. This review mainly entails changes due having higher number mutations. binding affinity, cellular entry, disease severity, infection rates, importantly, immune evading potential them discussed this review. A comparative analysis Delta other variants evolved before gives readers in-depth understanding landscape infection. Furthermore, discusses range abilities possessed approved antiviral therapeutic molecules neutralizing antibodies functional against sub-variants. evolution is causing infections, but broader aspect their not been explored. Thus, scientific should adopt elucidative approach obtain clear idea about recently including variants, so effective vaccines drugs can be achieved. This, turn, will lead drop cases and, finally, end pandemic.

Язык: Английский

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Applications of Molecular Dynamics Simulation in Protein Study

Membranes, Год журнала: 2022, Номер 12(9), С. 844 - 844

Опубликована: Авг. 29, 2022

Molecular Dynamics (MD) Simulations is increasingly used as a powerful tool to study protein structure-related questions. Starting from the early simulation on photoisomerization in rhodopsin 1976, MD has been function, stability, protein-protein interaction, enzymatic reactions and drug-protein interactions, membrane proteins. In this review, we provide brief review for history of application current status applications studies.

Язык: Английский

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SARS-CoV-2 evolved variants optimize binding to cellular glycocalyx

Cell Reports Physical Science, Год журнала: 2023, Номер 4(4), С. 101346 - 101346

Опубликована: Апрель 1, 2023

Viral variants of concern continue to arise for SARS-CoV-2, potentially impacting both methods detection and mechanisms action. Here, we investigate the effect an evolving spike positive charge in SARS-CoV-2 subsequent interactions with heparan sulfate angiotensin converting enzyme 2 (ACE2) glycocalyx. We show that positively charged Omicron variant evolved enhanced binding rates negatively Moreover, discover while spike-ACE2 affinity is comparable Delta variant, are significantly enhanced, giving rise a ternary complex spike-heparan sulfate-ACE2 large proportion double-bound triple-bound ACE2. Our findings suggest evolve be more dependent on viral attachment infection. This discovery enables us engineer second-generation lateral-flow test strip harnesses heparin ACE2 reliably detect all concern, including Omicron.

Язык: Английский

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Evolution of the SARS-CoV-2 Omicron spike

Cell Reports, Год журнала: 2023, Номер 42(12), С. 113444 - 113444

Опубликована: Ноя. 18, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. spike (S) protein accumulated an unprecedented number sequence changes relative to previous variants. In this review, we discuss how S structural features modulate host cell receptor binding, virus entry, immune evasion highlight these differentiate from We also examine key properties track across the still-evolving subvariants importance continuing surveillance evolution over time.

Язык: Английский

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SARS-CoV-2 Omicron Subvariants Do Not Differ Much in Binding Affinity to Human ACE2: A Molecular Dynamics Study

The Journal of Physical Chemistry B, Год журнала: 2024, Номер 128(14), С. 3340 - 3349

Опубликована: Апрель 2, 2024

The emergence of the variant concern Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exacerbates COVID-19 pandemic due to its high contagious ability. Studies have shown that binds human ACE2 more strongly than wild type. prevalence in new cases promotes novel lineages with improved receptor binding affinity and immune evasion. To shed light on this open problem, work, we investigated free energy domain BA.2, BA.2.3.20, BA.3, BA4/BA5, BA.2.75, BA.2.75.2, BA.4.6, XBB.1, XBB.1.5, BJ.1, BN.1, BQ.1.1, CH.1.1 using all-atom molecular dynamics simulation mechanics Poisson–Boltzmann surface area method. results show these increased compared BA.1 lineage, BA.2.75 BA.2.75.2 subvariants bind others. However, general, affinities do not differ significantly from each other. electrostatic force dominates over van der Waals interaction between cells. Based our results, argue viral evolution does further improve SARS-CoV-2 for but may increase

Язык: Английский

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Next-generation treatments: Immunotherapy and advanced therapies for COVID-19

Heliyon, Год журнала: 2024, Номер 10(5), С. e26423 - e26423

Опубликована: Фев. 19, 2024

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS recent decades, underscoring their high potential infectivity humans. Insights from previous have played a significant role developing effective strategies to mitigate the global impact SARS-CoV-2. As January 7, 2024, there been 774,075,242 confirmed cases worldwide. To date, 13.59 billion vaccine doses administered, 7,012,986 documented fatalities (https://www.who.int/)Despite progress addressing rapid evolution SARS-CoV-2 challenges human defenses, presenting ongoing challenges. emergence new lineages, shaped mutation recombination processes, has led successive waves infections. This scenario reveals need for next-generation vaccines as crucial requirement ensuring protection against demand calls formulations that trigger robust adaptive immune response without leading inflammation linked with infection.Key mutations detected Spike protein, critical target neutralizing antibodies design —specifically within Receptor Binding Domain region Omicron variant lineages (B.1.1.529), currently dominant worldwide, intensified concerns due association immunity evasion vaccinations infections.As world deals this evolving threat, narrative extends realm emerging variants, each displaying implications remain largely misunderstood. Notably, JN.1 lineage is gaining prevalence, early findings suggest it stands among immune-evading characteristic attributed its L455S. Moreover, detrimental consequences novel bear particularly on immunocompromised individuals older adults. Immunocompromised face such suboptimal responses vaccines, rendering them more susceptible disease. Similarly, adults an increased risk disease presence comorbid conditions, find themselves at heightened vulnerability develop Thus, recognizing these intricate factors effectively tailoring public health protect vulnerable populations. In context, review aims describe, analyze, discuss current treatments encompassing immunotherapeutic approaches advanced therapies complements will offer solutions counter disadvantages existing options. Preliminary outcomes show virus address immunomodulatory associated COVID-19. Furthermore, capacity promote tissue repair demonstrated, which can be noteworthy who stand actors landscape possess broader potential, offering wide range variants enhancing ability constant virus. are projected treatment alternatives managing Chronic Post-COVID-19 syndromeand long-term complications.

Язык: Английский

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Circular mRNA Vaccine against SARS-COV-2 Variants Enabled by Degradable Lipid Nanoparticles

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

The emergence of mRNA vaccines offers great promise and a potent platform in combating various diseases, notably COVID-19. Nevertheless, challenges such as inherent instability potential side effects current delivery systems underscore the critical need for advancement stable, safe, efficacious vaccines. In this study, robust vaccine (cmRNA-1130) eliciting immune activation has been developed from biodegradable lipid with eight ester bonds branched tail (AX4) synthetic circular (cmRNA) encoding trimeric Delta receptor binding domain SARS-CoV-2 spike protein. Notably, cmRNA-1130 exhibits outstanding stability, remaining effective after six months storage at 4 °C multiple freeze–thaw cycles. comparison commercial MC3 lipid, nanoparticles formed degradable AX4 revealed much faster metabolic rate liver spleen, affording negligible impairment to hepatorenal function. Following intramuscular administration, generates sustained neutralizing antibodies induces RBD-specific CD4+ CD8+ T effector memory cells (TEM) Th1-biased mice. Featured activation, high decent safety, cmRNA hold huge clinical prophylaxis treatment different diseases.

Язык: Английский

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SARS-CoV-2 Spike N-Terminal Domain Engages 9-O-Acetylated α2–8-Linked Sialic Acids

ACS Chemical Biology, Год журнала: 2023, Номер 18(5), С. 1180 - 1191

Опубликована: Апрель 27, 2023

SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the protein contains C-terminal binding (RBD) and an N-terminal (NTD). NTD other coronaviruses includes glycan cleft. However, for NTD, protein–glycan was only observed weakly sialic acids highly sensitive methods. Amino acid changes in variants concern (VoC) show antigenic pressure, which can be indication NTD-mediated binding. Trimeric proteins SARS-CoV-2, alpha, beta, delta, omicron did not reveal capability. Unexpectedly, beta subvariant strain (501Y.V2-1) to Vero E6 cells sialidase pretreatment. Glycan microarray analyses identified putative 9-O-acetylated ligand, confirmed by catch-and-release ESI-MS, STD-NMR analyses, graphene-based electrochemical sensor. variant attained enhanced modality specificity toward structures, suggesting dual-receptor functionality domain, quickly selected against. These results indicate that probe additional evolutionary space, allowing receptors on surface target cells.

Язык: Английский

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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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Is BF.7 more infectious than other Omicron subtypes: Insights from structural and simulation studies of BF.7 spike RBD variant

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 238, С. 124154 - 124154

Опубликована: Март 24, 2023

Язык: Английский

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