AlphaFold2 Predictions of Conformational Ensembles and Atomistic Simulations of the SARS-CoV-2 Spike XBB Lineages Reveal Epistatic Couplings between Convergent Mutational Hotspots that Control ACE2 Affinity

The Journal of Physical Chemistry B, Год журнала: 2024, Номер 128(19), С. 4696 - 4715

Опубликована: Май 2, 2024

In this study, we combined AlphaFold-based atomistic structural modeling, microsecond molecular simulations, mutational profiling, and network analysis to characterize binding mechanisms of the SARS-CoV-2 spike protein with host receptor ACE2 for a series Omicron XBB variants including XBB.1.5, XBB.1.5+L455F, XBB.1.5+F456L, XBB.1.5+L455F+F456L. dynamic modeling Spike lineages can accurately predict experimental structures conformational ensembles complexes ACE2. Microsecond dynamics simulations identified important differences in landscapes equilibrium variants, suggesting that combining AlphaFold predictions multiple conformations provide complementary approach characterization functional states mechanisms. Using ensemble-based profiling residues physics-based rigorous calculations affinities, energy hotspots characterized basis underlying epistatic couplings between convergent hotspots. Consistent experiments, results revealed mediating role Q493 hotspot synchronization L455F F456L mutations, providing quantitative insight into energetic determinants lineages. We also proposed network-based perturbation allosteric communications uncovered relationships centers long-range communication couplings. The study support mechanism which may be determined by effects evolutionary control binding.

Язык: Английский

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Broad-spectrum affinity chromatography of SARS-CoV-2 and Omicron vaccines from ligand screening to purification

Journal of Chromatography A, Год журнала: 2025, Номер 1743, С. 465685 - 465685

Опубликована: Янв. 17, 2025

Язык: Английский

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Decoding Omicron: Genetic Insight into Its Transmission Dynamics, Severity Spectrum and Ever-Evolving Strategies of Immune Escape in comparison with other SARS-CoV-2 variants.

Diagnostic Microbiology and Infectious Disease, Год журнала: 2025, Номер 111(3), С. 116705 - 116705

Опубликована: Янв. 23, 2025

Язык: Английский

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Neutralizing antibody responses to three XBB protein vaccines in older adults

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 2, 2025

Язык: Английский

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Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern

Vaccines, Год журнала: 2025, Номер 13(4), С. 424 - 424

Опубликована: Апрель 17, 2025

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating severity clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have developed to this effect, including BioNTech-Pfizer Moderna’s mRNA vaccines, as well adenovirus vector-based such Oxford–AstraZeneca. However, emergence new variants subvariants SARS-CoV-2, characterized by enhanced transmissibility immune evasion, poses significant challenges efficacy current vaccination strategies. In review, we aim comprehensively outline landscape emerging concern (VOCs) sub-lineages that recently surfaced post-pandemic years. We assess effectiveness existing their booster doses, against these subvariants, BA.2-derived sub-lineages, XBB BA.2.86 (Pirola). Furthermore, discuss latest advancements vaccine technology, multivalent pan-coronavirus approaches, along development several next-generation coronavirus exosome-based, virus-like particle (VLP), mucosal, nanomaterial-based vaccines. Finally, highlight key critical areas for future research address evolving threat develop strategies combating viral threats, thereby improving preparedness pandemics.

Язык: Английский

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Longitudinal Analysis of Humoral and Cellular Immune Response up to 6 Months after SARS-CoV-2 BA.5/BF.7/XBB Breakthrough Infection and BA.5/BF.7-XBB Reinfection

Vaccines, Год журнала: 2024, Номер 12(5), С. 464 - 464

Опубликована: Апрель 26, 2024

The rapid mutation of SARS-CoV-2 has led to multiple rounds large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes humoral cellular immunity responses several subvariants after remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, IFN-γ secreting CD4+/CD8+ T cell variants, we observed that each component exhibited distinct kinetics. Either induces relatively high level binding neutralizing titers against Omicron at an early time point, which rapidly decreases over time. Most 6 months post-breakthrough completely lost their activities BQ.1.1, CH.1.1, BA.2.86, JN.1 XBB subvariants. Individuals with exhibit imprinting shifting recall pre-existing BA.5/BF.7 neutralization antibodies. BA.5 group, frequency XBB.1.16-RBD specific cells, resting intermediate cells gradually increased On other hand, induced by WT/BA.5/XBB.1.16 spike trimer remains stable Overall, research indicates have declining levels but can provide some degree protection future exposure new antigens.

Язык: Английский

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A Review of Protein-Based COVID-19 Vaccines: From Monovalent to Multivalent Formulations

Vaccines, Год журнала: 2024, Номер 12(6), С. 579 - 579

Опубликована: Май 25, 2024

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in COVID-19 pandemic, has profoundly impacted global healthcare systems and trajectory economic advancement. As nations grapple with far-reaching consequences this unprecedented health crisis, administration vaccines proven to be a pivotal strategy managing crisis. Protein-based have garnered significant attention owing their commendable safety profile precise immune targeting advantages. Nonetheless, unpredictable mutations widespread transmission SARS-CoV-2 posed challenges for vaccine developers governments worldwide. Monovalent multivalent represent two strategies development, ongoing controversy surrounding efficacy. This review concentrates on development protein-based vaccines, specifically addressing transition from monovalent formulations, synthesizes data manufacturers, antigen composition, clinical study findings, other features that shape distinct profiles overall effectiveness. Our hypothesis is could offer enhanced capability broad-spectrum protection.

Язык: Английский

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Tannic acids and proanthocyanidins in tea inhibit SARS-CoV-2 variants infection

American Journal of Cancer Research, Год журнала: 2024, Номер 14(5), С. 2555 - 2569

Опубликована: Янв. 1, 2024

The COVID-19 pandemic has caused hundreds million cases and millions death as well continues to infect human life in the world since late of 2019. breakthrough infection from mutation SARS-CoV-2 is rising even vaccinated population been increasing. Currently, severe threat posed by alleviated worldwide, situation transitioned coexisting with virus. dietary food antiviral activities may improve prevent virus for living pandemic. Teas containing enriched phenolic ingredients such tannins have reported be antitumor agents good inhibitors coronavirus. This study developed a highly sensitive selective ultra-high performance liquid chromatography-high resolution mass spectrometric method quantification tannic acids, hydrolysable tannin, proanthocyanidins, condense teas different levels fermentation. vitro pseudoviral particles (Vpp) assay was used evaluate inhibition various teas. results current research demonstrate that are effective against its variants.

Язык: Английский

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Fourth dose bivalent COVID-19 vaccines outperform monovalent boosters in eliciting cross-reactive memory B cells to Omicron subvariants

Journal of Infection, Год журнала: 2024, Номер 89(4), С. 106246 - 106246

Опубликована: Авг. 8, 2024

Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging subvariants. Here, we characterized RBD-specific memory B cell (Bmem) response following a fourth dose with bivalent vaccine, in direct comparison WH1 monovalent dose. Healthcare workers previously immunized mRNA adenoviral vector were sampled before one month after vaccine. Serum neutralizing antibodies (NAb) quantified, as well Bmem an in-depth spectral flow cytometry panel including recombinant RBD proteins of WH1, BA.1, BA.5, BQ.1.1, XBB.1.5 variants. Both elicited higher NAb titers against subvariants compared Following either vaccine type, recipients had slightly increased numbers. significantly binding all tested by cytometry, while recognition was not vaccination. IgG1

Язык: Английский

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Lessons from COVID‐19: Aspects of prevention, therapeutics, and diagnostics against SARS‐CoV‐2 with special focus on JN.1 and XBB sublineages

MedComm – Future Medicine, Год журнала: 2024, Номер 3(2)

Опубликована: Июнь 1, 2024

Abstract The end of second decade in the 21st century witnessed a prominent disease outbreak caused by novel coronavirus SARS‐CoV‐2 (including most diverse omicron subvariants), where death toll crossed boundary 6.9 million across globe December 19, 2023. All spheres central dogma molecular biology and host‒pathogen interaction was explored to find ways diagnostics, isolation, curtailment, therapy. Above all, diagnostics therapeutics against COVID‐19 took an enormous jump, which needs be evaluated for accuracy feasibility requires serious compilation current future generations. With same objective, this review encompasses including prevention practiced proposed during handling pandemic globe. It involves role mutations viruses subsequent epitope mapping with potential immune escape mechanisms variants conservancy T‐cell epitopes has also been highlighted. efficacy antigen/antibody‐based RT‒PCR‐ NGS‐based confirmation pathogen presence, imaging (X‐ray/CT‐scan) symptoms damage assessment thoroughly filtered. possibility errors their cause consequences have presented ease readers further improvisers.

Язык: Английский

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