Broad Neutralization Capacity of an Engineered Thermostable Three-Helix Angiotensin-Converting Enzyme 2 Polypeptide Targeting the Receptor-Binding Domain of SARS-CoV-2 DOI Open Access
Davide Cavazzini, Elisabetta Levati, S. Germani

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12319 - 12319

Опубликована: Ноя. 16, 2024

The mutational drift of SARS-CoV-2 and the appearance multiple variants, including latest Omicron variant its sub-lineages, has significantly reduced (and in some cases abolished) protective efficacy Wuhan spike-antigen-based vaccines therapeutic antibodies. One most functionally constrained thus largely invariable regions spike protein is one involved interaction with ACE2 receptor mediating cellular entry SARS-CoV-2. Engineered ACE2, both as a full-length or an engineered polypeptide fragment, been shown to be capable preventing host-cell binding all viral variants endowed potent neutralization activity vitro vivo. Here, we report on biochemical antiviral properties rationally designed N-terminal, three-helix fragments that retain native-like conformation. these fragments, designated PRP8_3H produced recombinant form, bears structure-stabilizing binding-affinity enhancing mutations α-helix-I α-helix I II, respectively. While native-like, unmodified three α-helices fragment proved thermally unstable without any detectable pseudovirion capacity, was found highly thermostable receptor-binding domain nanomolar affinity neutralize spike-expressing pseudovirions at (sub)micromolar concentrations. lends itself promising decoy prototype suitable for variety formulations prophylactic applications.

Язык: Английский

Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort DOI Creative Commons

Gerald Kevin Oluka,

Jackson Sembera,

Joseph Ssebwana Katende

и другие.

Vaccines, Год журнала: 2025, Номер 13(2), С. 143 - 143

Опубликована: Янв. 29, 2025

Background: This study assessed the long-term dynamics of neutralizing antibodies in a Ugandan cohort primarily exposed to A.23.1 SARS-CoV-2 variant, examining how this shaped immune breadth and potency against diverse strains following infection prototype-based vaccination. Methods: We conducted 427-day retrospective analysis 41 participants across multiple waves, assessing binding antibody responses using in-house ELISA pseudotyped virus neutralization assays. quantified key variants, A.23.1, D614G, Delta, BA.4, capturing evolving immunity pandemic. Results: Neutralizing titers remained significantly higher than those highlighting solid memory infection. Consistently lower were observed for BA.4 all time points, aligning with its strong immune-evasion capability. Correlations between spike-directed IgG (S-IgG) concentrations stronger no correlation BA.4. ChAdOx1-S vaccination substantially elevated most notably essential role boosting immunity, even individuals initially low titers. Conclusions: Initial exposure variant triggered potent responses, shaping during subsequent exposures. These findings highlight importance accounting early viral exposures vaccine development public health planning. The distinctly response highlights need continuous antigenic monitoring timely updates protection emerging variants. Vaccination remains reinforcing sustaining

Язык: Английский

Процитировано

1
Multiple Exposures to SARS-CoV-2 Spike enhance Cross-Reactive Antibody-Dependent Cellular Cytotoxicity against SARS-CoV-1 DOI
Guillaume Beaudoin-Bussières, Alexandra Tauzin,

Katrina Dionne

и другие.

Virology, Год журнала: 2025, Номер 607, С. 110512 - 110512

Опубликована: Март 22, 2025

Язык: Английский

Процитировано

0
Monitoring reported SARS-CoV-2 variants to assess the status of COVID-19 epidemics in the low epidemic state DOI Creative Commons
Bin Liu, Zhongliang Wang, Shanshan Lu

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 24, 2025

The reported new confirmed cases of Coronavirus Disease 2019 (COVID-19) nowadays have diminished in their usefulness for assessing the pandemic situation. This study aimed to discover correlation Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) variants recorded by Nextstrain clade and PANGO lineage number cases. Percent stacked area charts were utilized display development trends. 31 1452 named according lineage, respectively. branch step value maintained a stable increase linear regression analysis. changing trend SARS-CoV-2 (PANGO lineage) correlated negatively with COVID-19 through Spearman rank coefficient (17/06/2020-17/11/2021, ρ=-0.387, P < 0.01; 15/12/2021-11/01/2023, ρ=-0.458, 0.01). proportion composition dominant virus had regional discrepancies, but some also fluctuated. speed quantity objectively reflect characteristics viral dissemination population even without valuable data variation may be better tool epidemic monitoring early-warning low state.

Язык: Английский

Процитировано

0
Genomic Evolution of the SARS-CoV-2 Omicron Variant in Córdoba, Argentina (2021–2022): Analysis of Uncommon and Prevalent Spike Mutations DOI Creative Commons
Nadia B. Olivero,

Victoria E. Zappia,

Pablo R. Gargantini

и другие.

Viruses, Год журнала: 2024, Номер 16(12), С. 1877 - 1877

Опубликована: Дек. 3, 2024

Understanding the evolutionary patterns and geographic spread of SARS-CoV-2 variants, particularly Omicron, is essential for effective public health responses. This study focused on genomic analysis Omicron variant in Cordoba, Argentina from 2021 to 2022. Phylogenetic revealed dominant presence BA.1 BA.2 lineages, with BA.5 emerging earlier than BA.4, aligning observations other regions. Haplotype network showed significant genetic divergence within samples, forming distinct clusters. In comparison global datasets, we identified mutations genomes (A27S, Y145D, L212I) situated NTD region Spike protein. These mutations, while not widespread globally, higher prevalence our region. Of particular interest were Y145D L212I substitutions, previously unreported Argentina. silico that both impact binding affinity T-cell epitopes HLA type I II alleles. Notably, these alleles are among most common Argentinian population, some associated protection against others susceptibility infection. findings strongly suggest prevalent likely influence immunogenicity protein contribute immune evasion mechanisms. provides valuable insights into dynamics highlights unique potential implications COVID-19 vaccines.

Язык: Английский

Процитировано

1
Is Antimicrobial Stewardship Policy Effectively Implemented in Polish Hospitals? Results from Antibiotic Consumption Surveillance before and during the COVID-19 Pandemic DOI Creative Commons
Urszula Durlak, Cezary Kapturkiewicz, Anna Różańska

и другие.

Antibiotics, Год журнала: 2024, Номер 13(7), С. 636 - 636

Опубликована: Июль 10, 2024

The COVID-19 pandemic posed numerous challenges to public health systems, particularly in antimicrobial stewardship. This study aimed assess antibiotic consumption before and during the evaluate effectiveness of implemented stewardship program.

Язык: Английский

Процитировано

0
Broad Neutralization Capacity of an Engineered Thermostable Three-Helix Angiotensin-Converting Enzyme 2 Polypeptide Targeting the Receptor-Binding Domain of SARS-CoV-2 DOI Open Access
Davide Cavazzini, Elisabetta Levati, S. Germani

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12319 - 12319

Опубликована: Ноя. 16, 2024

The mutational drift of SARS-CoV-2 and the appearance multiple variants, including latest Omicron variant its sub-lineages, has significantly reduced (and in some cases abolished) protective efficacy Wuhan spike-antigen-based vaccines therapeutic antibodies. One most functionally constrained thus largely invariable regions spike protein is one involved interaction with ACE2 receptor mediating cellular entry SARS-CoV-2. Engineered ACE2, both as a full-length or an engineered polypeptide fragment, been shown to be capable preventing host-cell binding all viral variants endowed potent neutralization activity vitro vivo. Here, we report on biochemical antiviral properties rationally designed N-terminal, three-helix fragments that retain native-like conformation. these fragments, designated PRP8_3H produced recombinant form, bears structure-stabilizing binding-affinity enhancing mutations α-helix-I α-helix I II, respectively. While native-like, unmodified three α-helices fragment proved thermally unstable without any detectable pseudovirion capacity, was found highly thermostable receptor-binding domain nanomolar affinity neutralize spike-expressing pseudovirions at (sub)micromolar concentrations. lends itself promising decoy prototype suitable for variety formulations prophylactic applications.

Язык: Английский

Процитировано

0