Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic DOI Creative Commons
Emil Bach, Mustafa Ghanizada,

Nikolaj Kirkby

et al.

Open Research Europe, Journal Year: 2024, Volume and Issue: 4, P. 215 - 215

Published: Oct. 11, 2024

Background Antibodies play a key role in the immune defence against infectious pathogens. Understanding underlying process of B cell recognition is not only fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas conformational epitope complicated to decipher, linear epitopes offer straightforward approach that can be reduced peptide recognition. Methods We utilised an overlapping encompassing proteomes seven human-infecting coronaviruses. Pooled sera from eight PCR-confirmed COVID-19 convalescents pre-pandemic controls were analysed. 13-mer peptides by 11 amino acids synthesised incubated with pooled sera. Fluorochrome-labelled anti-IgG -IgA antibodies applied detect antibody-peptide interactions. Strong antibody interactions spanning consecutive identified as 'high-fidelity regions' (HFRs) mapped coronavirus using 60% homology threshold for clustering. Results found 333 HFRs derived human Among these, 98 (29%) SARS-CoV-2, 144 (44%) one or more common cold coronaviruses (CCC), 54 (16%) cross-mapped both SARS-CoV-2 CCCs. The remaining 37 (11%) either SARS-CoV MERS-CoV. Notably, serum favoured SARS-CoV-2-mapped HFRs, while CCC-mapped HFRs. primary targets ORF1ab protein (60%), spike (21%), nucleoprotein (15%) absolute numbers; however, order was reversed terms density. Conclusion across coronaviruses, highlighting pan-, alpha-, beta-, SARS-CoV-2-corona-specific patterns. These insights could aid understanding past present exposures. Additionally, our results indicate potential cross-reactivity anti-CCC possibly influencing outcomes. Lastly, methodology offers rapid thorough high-resolution B-cell mapping, which crucial future studies emerging diseases.

Language: Английский

SARS-CoV-2 Vaccines: The Advantage of Mucosal Vaccine Delivery and Local Immunity DOI Creative Commons
Joshua Tobias, Peter Steinberger,

Joy Wilkinson

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(7), P. 795 - 795

Published: July 18, 2024

Immunity against respiratory pathogens is often short-term, and, consequently, there an unmet need for the effective prevention of such infections. One infectious disease coronavirus 19 (COVID-19), which caused by novel Beta SARS-CoV-2 that emerged around end 2019. The World Health Organization declared illness a pandemic on 11 March 2020, and since then it has killed or sickened millions people globally. development COVID-19 systemic vaccines, impressively led to significant reduction in severity, hospitalization, mortality, contained pandemic’s expansion. However, these vaccines have not been able stop virus from spreading because restricted mucosal immunity. As result, breakthrough infections frequently occurred, new strains emerging. Furthermore, will likely continue circulate like influenza virus, co-exist with humans. upper tract nasal cavity are primary sites infection thus, mucosal/nasal vaccination induce response virus’ transmission warranted. In this review, we present status both approved those under evaluation clinical trials. our approach B-cell peptide-based applied prime-boost schedule elicit

Language: Английский

Citations

5
Investigating the Post-Mortem Risk of Transmission of SARS-CoV-2 Virus in Cadaveric Tissues: A Systematic Review of the Literature DOI Creative Commons
Matteo Antonio Sacco,

Saverio Gualtieri,

Aurora Princi

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(2), P. 284 - 284

Published: Jan. 27, 2025

The emergence of SARS-CoV-2, responsible for the COVID-19 pandemic, has prompted extensive research into its transmission dynamics; yet, a critical aspect that remains underexplored is post-mortem infectivity virus within cadaveric tissues. Understanding mechanisms by which SARS-CoV-2 maintains after death essential, as it raises significant concerns regarding public health and forensic practices. Research indicates can persist in various tissues, including lung, liver, kidney with studies showing factors such time elapsed since death, presence underlying conditions, environmental conditions at influence level deceased individuals. These findings are not only crucial establishing safety protocols investigators who handle cadavers but also informing guidelines govern management bodies during outbreaks. As we investigate implications infectivity, becomes imperative to establish comprehensive mitigate risks associated handling disposal infected bodies, thereby protecting ensuring those working environments. This paper aims elucidate explore persistence tissue types, assess broader investigations, ultimately contributing safer approach dealing COVID-19-related fatalities.

Language: Английский

Citations

0
Molecular mechanistic exploration of conformational shifts induced by class IV anti-RBD antibody IY2A DOI
Enhao Zhang, Song Luo,

Xiaole Xu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 141417 - 141417

Published: Feb. 1, 2025

Language: Английский

Citations

0
Cleaved vs. Uncleaved: How Furin Cleavage Reshapes the Conformational Landscape of SARS-CoV-2 Spike DOI Creative Commons

Natesan Mani,

Raghavendran Suresh,

Srirupa Chakraborty

et al.

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

Published: March 14, 2025

The SARS-CoV-2 Spike protein is the primary target for vaccine design, with immunogens typically engineered to enhance stability by introducing proline mutations (2P) and mutating or deleting Furin Cleavage Site (FCS). While these modifications improve structural integrity, studies suggest that furin cleavage can play a functional role in dynamics, potentially enhancing ACE2 receptor binding. However, impact of this on unbound form remains unclear. In study, we use extensive all-atom molecular dynamics (MD) simulations compare dynamic properties cleaved uncleaved proteins their pre-fusion, state. Our results show significantly alters allosteric communication within protein, increasing correlated motions between Receptor Binding Domain (RBD) N-terminal (NTD), which may facilitate engagement. Principal Component Analysis (PCA) reveals sample distinct conformational landscapes, displaying enhanced flexibility broader range RBD tilt angles. Additionally, primes S2 subunit expanding central helix, influencing transition post-fusion Glycan clustering patterns further an adaptive response cleavage, particularly NTD regions. These findings highlight potential consequences FCS deletion immunogen design underscore importance considering native state therapeutic development.

Language: Английский

Citations

0
Why Should Vaccines against Respiratory Diseases Go Mucosal? B Cell Epitope-Based Vaccines against SARS-CoV-2 DOI Open Access
Joshua Tobias, Peter Steinberger,

Joy Wilkinson

et al.

Published: June 13, 2024

Immunity against respiratory pathogens is often short-term, and consequently there an unmet need for effective prevention of such infections. One infectious disease COVID-19, which caused by the novel Beta coronavirus SARS-CoV-2 that emerged around end 2019. The World Health Organization declared illness a pandemic on March 11, 2020, since then it has killed or sickened millions people globally. development COVID-19 systemic vaccines, impressively led to significant reduction in severity, hospitalization, mortality, con-tained pandemic's expansion. However, these vaccines have not been able stop virus from spreading because restricted mucosal immunity. As result, breakthrough infections frequently occurred new strains emerging. Furthermore, will likely continue circulate and, like influenza virus, co-exist with humans. upper tract nasal cavity are primary sites infection thus, mucosal/nasal vaccination induce response transmission warrant-ed. In this review, we present status approved those under evaluation clinical trials. our approach B-cell pep-tide-based applied prime-boost schedule eliciting both

Language: Английский

Citations

1
Unraveling the structural and functional dimensions of SARS-CoV2 proteins in the context of COVID-19 pathogenesis and therapeutics DOI

Aniruddh Jhanwar,

Dipika Sharma,

Uddipan Das

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 278, P. 134850 - 134850

Published: Aug. 22, 2024

Language: Английский

Citations

1
Entry of Enveloped Viruses into Host Cells: Membrane Fusion DOI
Vicente Más, José A. Melero

Sub-cellular biochemistry/Subcellular biochemistry, Journal Year: 2024, Volume and Issue: unknown, P. 567 - 592

Published: Jan. 1, 2024

Language: Английский

Citations

1
Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic DOI Open Access
Emil Bach, Mustafa Ghanizada,

Nikolaj Kirkby

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Abstract Background Antibodies play a key role in the immune defence against infectious pathogens. Understanding underlying process of B cell recognition is not only fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas nature conformational epitope inherently complicated, linear epitopes offer straightforward approach that potentially can be reduced to one peptide recognition. Methods Using an overlapping representing entire proteomes seven main coronaviruses known infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents pre-pandemic controls. high-density microarray platform, 13-mer peptides by 11 amino acids were situ synthesised incubated with primary serum samples, followed development secondary fluorochrome-labelled anti-IgG -IgA antibodies. Interactions detected fluorescence detection. Strong Ig interactions encompassing consecutive considered represent “high-fidelity regions” (HFRs). These mapped coronavirus using 60% homology threshold for clustering. Results We identified 333 human derived HFRs. Among these, 98 (29%) SARS-CoV-2, 144 (44%) or more four circulating common cold (CCC), 54 (16%) cross-mapped both SARS-CoV-2 CCCs. The remaining 37 (11%) either SARS-CoV MERS-CoV. Notably, was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas CCC-mapped In terms absolute numbers epitopes, targets are ORF1ab protein (60%), spike (21%), nucleoprotein (15%) order; however, density order would reversed. Conclusion across coronaviruses, highlighting pan-, alpha-, beta-, SARS-CoV-2-corona-specific patterns. findings could pivotal deciphering past current exposures epidemic endemic coronavirus. Moreover, our results suggest anti-CCC antibodies may cross-react which explain highly variable outcome COVID-19. Finally, methodology used here offers rapid comprehensive high-resolution B-cell mapping, vital future studies emerging diseases.

Language: Английский

Citations

0
Prone-to-Infectivity of Omicron BA.2 Subvariant from Indonesia on ACE-2 Expressing Cell Lines DOI Creative Commons

Wahyu Hidayati,

Desti Hidayati,

Fathur Luthfiano Khairindra

et al.

Journal of Advanced Research in Micro and Nano Engieering, Journal Year: 2024, Volume and Issue: 21(1), P. 54 - 65

Published: July 31, 2024

SARS-CoV-2 virus undergoes mutation, leading to the virus's evolution and modifications in characteristics of virus. Omicron, including BA.2 subvariant, is currently predominant variant infection. There are no reports regarding its properties or utilization Indonesian isolate for therapy vaccine development. Therefore, this study evaluated appropriate host cells Omicron via susceptibility tests. The from Indonesia was exposed three mammalian-ACE2-expressing cell lines. Sharing amino acids between previous VOC subvariants performed using a simple silico comparison method. results showed that could not infect HepG2 Huh-7D12 due foci forming on those Moreover, we also found has unique acid alteration spike protein. According findings, propagate Vero E6 lines, mutations play role changing infection mechanism. A deeper vitro experiment enhance findings by comparing all sequences analyzing mechanism each single mutation pseudovirus.

Language: Английский

Citations

0
Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic DOI Creative Commons
Emil Bach, Mustafa Ghanizada,

Nikolaj Kirkby

et al.

Open Research Europe, Journal Year: 2024, Volume and Issue: 4, P. 215 - 215

Published: Oct. 11, 2024

Background Antibodies play a key role in the immune defence against infectious pathogens. Understanding underlying process of B cell recognition is not only fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas conformational epitope complicated to decipher, linear epitopes offer straightforward approach that can be reduced peptide recognition. Methods We utilised an overlapping encompassing proteomes seven human-infecting coronaviruses. Pooled sera from eight PCR-confirmed COVID-19 convalescents pre-pandemic controls were analysed. 13-mer peptides by 11 amino acids synthesised incubated with pooled sera. Fluorochrome-labelled anti-IgG -IgA antibodies applied detect antibody-peptide interactions. Strong antibody interactions spanning consecutive identified as 'high-fidelity regions' (HFRs) mapped coronavirus using 60% homology threshold for clustering. Results found 333 HFRs derived human Among these, 98 (29%) SARS-CoV-2, 144 (44%) one or more common cold coronaviruses (CCC), 54 (16%) cross-mapped both SARS-CoV-2 CCCs. The remaining 37 (11%) either SARS-CoV MERS-CoV. Notably, serum favoured SARS-CoV-2-mapped HFRs, while CCC-mapped HFRs. primary targets ORF1ab protein (60%), spike (21%), nucleoprotein (15%) absolute numbers; however, order was reversed terms density. Conclusion across coronaviruses, highlighting pan-, alpha-, beta-, SARS-CoV-2-corona-specific patterns. These insights could aid understanding past present exposures. Additionally, our results indicate potential cross-reactivity anti-CCC possibly influencing outcomes. Lastly, methodology offers rapid thorough high-resolution B-cell mapping, which crucial future studies emerging diseases.

Language: Английский

Citations

0