Subsequent Waves of Convergent Evolution in SARS-CoV-2 Genes and Proteins

Vaccines, Год журнала: 2024, Номер 12(8), С. 887 - 887

Опубликована: Авг. 5, 2024

Beginning in 2022, following widespread infection and vaccination among the global population, SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines past infections. This review covers convergent evolution of structural, nonstructural, accessory proteins SARS-CoV-2, with a specific look at common mutations found long-lasting infections that hint potentially reverting an enteric sarbecovirus type.

Язык: Английский

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Structural and Functional Impacts of SARS-CoV-2 Spike Protein Mutations: Insights from Predictive Modeling and Analytics (Preprint)

Опубликована: Март 8, 2025

The COVID-19 pandemic requires a deep understanding of SARS-CoV-2, particularly how mutations in the Spike Receptor Binding Domain (RBD) Chain E affect its structure and function. Current methods lack comprehensive analysis these at different structural levels. To analyze impact specific associated point (N501Y, L452R, N440K, K417N, E484A) on SARS-CoV-2 RBD function using predictive modeling, including graph-theoretic model, protein modeling techniques, molecular dynamics simulations. study employed multi-tiered framework to represent across three interconnected This model incorporated 19 top-level vertices, connected intermediate graphs based 6-angstrom proximity within protein's 3D structure. Graph-theoretic metrics were applied weigh vertices edges all also used Iterative Threading Assembly Refinement (I-TASSER) mutated sequences dynamic simulation (MD) tools evaluate changes folding stability compared wildtype. Three distinct analytical approaches successfully identified functional (Chain E) resulting from mutations. novel detected notable changes, with N501Y L452R showing most pronounced effects conformation stability. K147N E484A demonstrated less significant impacts. Ab initio MD findings corroborated analysis. multi-level approach provided visualization mutation effects, deepening our their consequences. advanced implications. multi-faceted characterized various mutations, identifying as having substantial have important implications for vaccine development, therapeutic design, variant monitoring. research underscores power combining multiple virology, contributing valuable knowledge ongoing efforts against providing future studies viral impacts

Язык: Английский

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In Silico Design of miniACE2 Decoys with In Vitro Enhanced Neutralization Activity against SARS-CoV-2, Encompassing Omicron Subvariants

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10802 - 10802

Опубликована: Окт. 8, 2024

The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as October 2024, continuous evolution variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections severe illnesses, contributing viral evolution. These cases increase risk new emerging. This study explores miniACE2 decoys novel strategy counteract variants. Using silico design molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity receptor-binding domain multiple than naturally soluble human ACE2. BPs expressed E. coli tested vitro, showing promising neutralizing effects. Notably, BP9 exhibited an average IC50 4.9 µg/mL across several variants, including Wuhan strain, Mu, Omicron BA.1, BA.2 low demonstrates potent ability BP9, indicating its efficacy at concentrations.Based on these findings, emerged therapeutic candidate combating evolving thereby positioning it potential emergency biopharmaceutical.

Язык: Английский

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Second booster dose improves antibody neutralization against BA.1, BA.5 and BQ.1.1 in individuals previously immunized with CoronaVac plus BNT162B2 booster protocol

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Апрель 4, 2024

Introduction SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough avoid emergence of variants capable evading immune response induced by prior infections vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 BQ.1.1, antibody a cohort vaccinated with two doses CoronaVac protocol followed heterologous booster doses. Methods To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 18 months after protocol). For each point, individuals divided into subgroups, based on number additional received (No booster, 1 2 boosters), viral microneutralization assay performed evaluate neutralization titers seroconvertion rate. Results The findings presented here show that, despite first at 9m improved level omicron ancestor BA.1 (133.1 663.3), this trend significantly lower for BQ.1.1 (132.4 199.1, 63.2 100.2, respectively). However, 18m administration second dose considerably neutralization, observed only (2361.5), also subvariants (726.1) (659.1). Additionally, our data showed rate decayed over (93.3% 12m 68.4% 18m), completely recovered (95% 18m). Discussion Our reinforces concerns about immunity evasion subvariants, where less neutralized vaccine antibodies than BA.1. On other hand, enhanced capacity these subvariants. It is likely as new continue emerge, immunizations will be needed time.

Язык: Английский

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