SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 17 - 17

Published: Dec. 28, 2024

The COVID-19 pandemic, driven by the rapid evolution of SARS-CoV-2 virus, presents ongoing challenges to global public health. is characterized rapidly evolving mutations, especially in (but not limited to) spike protein, complicating predictions about its evolutionary trajectory. These mutations have significantly affected transmissibility, immune evasion, and vaccine efficacy, leading multiple pandemic waves with over half a billion cases seven million deaths globally. Despite several strategies, from development administration design availability antivirals, including monoclonal antibodies, already having been employed, persistent circulation virus emergence new variants continue result high case numbers fatalities. In past four years, immense research efforts contributed much our understanding viral pathogenesis mechanism, syndrome, host-microbe interactions, effective vaccines, diagnostic tools, treatments. focus this review provide comprehensive analysis functional impact on diagnosis, treatments, effectiveness. We further discuss safety pregnancy implications hybrid immunity long-term protection against infection, as well latest developments pan-coronavirus nasal formulations, emphasizing need for continued surveillance, research, adaptive health strategies response race.

Language: Английский

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Exploring Diverse Binding Mechanisms of Broadly Neutralizing Antibodies S309, S304, CYFN-1006 and VIR-7229 Targeting SARS-CoV-2 Spike Omicron Variants: Integrative Computational Modeling Reveals Balance of Evolutionary and Dynamic Adaptability in Shaping Molecular Determinants of Immune Escape

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract Evolution of SARS-CoV-2 has led to the emergence variants with increased immune evasion capabilities, posing significant challenges antibody-based therapeutics and vaccines. The cross-neutralization activity antibodies against Omicron is governed by a complex delicate interplay multiple energetic factors interaction contributions. In this study, we conducted comprehensive analysis interactions between receptor-binding domain (RBD) spike protein four neutralizing S309, S304, CYFN1006, VIR-7229. Using integrative computational modeling that combined all-atom molecular dynamics (MD) simulations, mutational scanning, MM-GBSA binding free energy calculations, elucidated structural, energetic, dynamic determinants antibody binding. Our findings reveal distinct mechanisms evolutionary adaptation driving broad neutralization effect these antibodies. We show S309 targets conserved residues near ACE2 interface, leveraging synergistic van der Waals electrostatic interactions, while S304 focuses on fewer but sensitive residues, making it more susceptible escape mutations. CYFN-1006.1 CYFN-1006.2 highlights epitope coverage critical anchors at T345, K440, T346, enhancing its efficacy carrying K356T mutation which caused from broadly potent VIR-7229 XBB.1.5 EG.5 emphasized large structurally epitope, demonstrating certain adaptability compensatory effects F456L L455S Mutational profiling identified key crucial for binding, including P337, R346 T385 K386 underscoring their roles as "weak spots" balance viral fitness evasion. results demonstrate good agreement predicted hotspots mutations respect latest experiments average scores. study dissect importance targeting diverse epitopes counteract resistance. Broad-spectrum CYFN1006 maintain across achieve convergent evolution enabling tolerance in positions through structural interface. underscore diversity employed different basis high affinity excellent generation

Language: Английский

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Antibody evasion associated with the RBD significant mutations in several emerging SARS-CoV-2 variants and its subvariants

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101008 - 101008

Published: Sept. 22, 2023

Language: Английский

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Another variant another history: description of the SARS-CoV-2 KP.2 (JN.1.11.1.2) mutations

Infectious Diseases, Journal Year: 2024, Volume and Issue: 56(7), P. 581 - 585

Published: May 29, 2024

Language: Английский

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Recent SARS-CoV-2 evolution trajectories indicate the emergence of Omicron’s several subvariants and the current rise of KP.3.1.1 and XEC

Virology, Journal Year: 2025, Volume and Issue: unknown, P. 110508 - 110508

Published: March 1, 2025

Language: Английский

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Distinctive Features of the XBB.1.5 and XBB.1.16 Spike Protein Receptor-Binding Domains and Their Roles in Conformational Changes and Angiotensin-Converting Enzyme 2 Binding

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12586 - 12586

Published: Aug. 9, 2023

The emergence and the high transmissibility of XBB.1.5 XBB.1.16 subvariants SARS-CoV-2 omicron has reignited concerns over potential impact on vaccine efficacy for these future variants. We investigated roles mutations structure spike protein’s receptor-binding domain (RBD) its interactions with host cell receptor ACE2. To bind to ACE2, RBD must transition from closed-form open-form configuration. found that XBB variants have less stable structures may make easier. enhance RBD–ACE2 in compared XBB.1.5. observed significant structural changes loop motif regions RBD, altering well-known antibody-binding sites potentially rendering primary RBD-specific antibodies ineffective. Our findings elucidate how subtle contribute subvariants’ fitness their predecessors.

Language: Английский

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Engineered Multivalent Nanobodies Efficiently Neutralize SARS-CoV-2 Omicron Subvariants BA.1, BA.4/5, XBB.1 and BQ.1.1

Vaccines, Journal Year: 2024, Volume and Issue: 12(4), P. 417 - 417

Published: April 15, 2024

Most available neutralizing antibodies are ineffective against highly mutated SARS-CoV-2 Omicron subvariants. Therefore, it is crucial to develop potent and broad-spectrum alternatives effectively manage Here, we constructed a high-diversity nanobody phage display library identified nine nanobodies specific the receptor-binding domain (RBD). Five of them exhibited cross-neutralization activity wild-type (WT) strain subvariants BA.1 BA.4/5, one demonstrated marked efficacy even BQ.1.1 XBB.1. To enhance therapeutic potential, engineered panel multivalent with increased potency breadth. The most nanobody, B13-B13-B13, cross-neutralized all tested pseudoviruses, geometric mean 50% inhibitory concentration (GM IC50) value 20.83 ng/mL. An analysis mechanism underlying enhancement neutralization breadth by representative that strategic engineering approach combining two or three into molecule could improve affinity between single spike, tolerance toward escape mutations such as R346T N460K. Our may be promising drug candidates for treating preventing infection future variants.

Language: Английский

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The diversification of SARS-CoV-2 Omicron variants and evaluation of their detection with molecular and rapid antigen assays

Journal of Clinical Virology, Journal Year: 2023, Volume and Issue: 166, P. 105532 - 105532

Published: July 6, 2023

The SARS-CoV-2 pandemic saw the rapid rise, global spread, and diversification of omicron variant in 2022. Given overwhelming dominance this globally its diverse lineages, there is an urgent need to ensure that diagnostic assays are capable detecting widely circulating sub-lineages. Remnant clinical VTM samples from PCR confirmed infections (n=733) collected Wisconsin (n=94), New York (n=267), South Carolina (n=372) throughout 2022 were sequenced, classified, tested with m2000 RealTime SARS-CoV-2, Alinity m ID NOW COVID-19 v2.0, BinaxNOW Ag Card, Panbio Rapid Test Device assays. Sequences lineage classifications obtained for n=641/733 (87.4%) included delta (n=6) representatives all major variants (BA.1, BA.2, BA.3, BA.4, BA.5, BE, BF, BQ.1, XBB). Panels lineages by molecular (n=624), (n=80), v2.0 (n=88) results showing 100% detection samples. had sensitivities 494/533 (92.7%) 416/469 (88.7%), respectively specimens >4 log10 copies/test, consistent expected performance frozen specimens. Furthermore, demonstrated 1-4 days, up 18 days post-symptom onset BA.1 infected patients copies/test. This data highlights rise over course demonstrate each 5 can detect breadth globally.

Language: Английский

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Engineered Therapeutic Antibody Against SARS-CoV-2

Current Clinical Microbiology Reports, Journal Year: 2023, Volume and Issue: 10(4), P. 222 - 235

Published: Nov. 14, 2023

Language: Английский

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