Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile DOI Open Access
Dongxia Wang, Zijian Zhang,

Jakub Baudys

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 23, 2023

Abstract SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics disulfide bonding of recombinant derived from Omicron variant (B.1.1.529) in comparison with D614G variant. Furthermore, conducted microsecond-long molecular dynamics simulations on resolve how different N-glycans impact conformational sampling two variants. Our findings reveal that protein maintains an overall resemblance terms site-specific glycan processing bond formation. Nonetheless, alterations glycans were observed at certain sites. These changes, synergy mutations within protein, result increased surface accessibility macromolecule, including ectodomain, receptor-binding domain, N-terminal domain. insights contribute our understanding interplay between structure function, thereby advancing effective vaccination therapeutic strategies. Teaser Through spectrometry simulations, is found be less covered by when compared

Language: Английский

Subtle Changes at the RBD/hACE2 Interface During SARS-CoV-2 Variant Evolution: A Molecular Dynamics Study DOI Creative Commons
Aria Gheeraert, Vincent Leroux, Dominique Mias‐Lucquin

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 541 - 541

Published: April 7, 2025

The SARS-CoV-2 Omicron variants show different behavior compared to the previous variants, especially with respect Delta variant, which promotes a lower morbidity despite being much more contagious. In this perspective, we performed molecular dynamics (MD) simulations of spike RBD/hACE2 complexes corresponding WT, and four variants. Carrying out comprehensive analysis residue interactions within between two partners allowed us draw profile each variant by using complementary methods (PairInt, hydrophobic potential, contact PCA). PairInt calculations highlighted residues most involved in electrostatic interactions, make strong contribution binding highly stable RBD hACE2. Apolar contacts made substantial detection patches. Contact networks cross-correlation matrices were able detect subtle changes at point mutations as S375F mutation occurring all is likely confer an advantage stability. This study brings new highlights on dynamic hACE2, may explain final persistence over Delta.

Language: Английский

Citations

0
Sialic Acids in Health and Disease DOI Creative Commons
Gerardo N. Guerrero-Flores,

Fayth M. Butler,

Verónica L. Martínez‐Marignac

et al.

Biologics, Journal Year: 2025, Volume and Issue: 5(2), P. 10 - 10

Published: March 26, 2025

Vertebrate cell surfaces exhibit intricate arrangements of glycosaminoglycan polymers, which are primarily linked to lipids and proteins. Numerous soluble secreted proteins also decorated with either individual sugar molecules or their polymers. The carbohydrate polymers commonly possess terminal nine-carbon sugars, known as sialic acids. Due widespread distribution strategic positioning, acids play a crucial role in mediating regulating wide range physiologic processes pathologic conditions. Human- animal-based investigations predominantly concentrate on the effects during infections, inflammations, vascular disorders, cancers. Further encompass variety applications, including cell–cell interactions, signaling, host–pathogen other biological functions associated nutrition, metabolism, genetic disorders. Nevertheless, future mechanistic needed clarify specific roles these varied contexts, so that more effective interventions may be developed.

Language: Английский

Citations

0
Enhanced Surface Accessibility of SARS-CoV-2 Omicron Spike Protein Due to an Altered Glycosylation Profile DOI Creative Commons
Dongxia Wang, Zijian Zhang,

Jakub Baudys

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(6), P. 2032 - 2046

Published: May 10, 2024

SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding in proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics disulfide bonding of recombinant derived from Omicron variant (B.1.1.529) comparison with D614G variant. Furthermore, conducted microsecond-long molecular dynamics simulations on resolve how different N-glycans impact conformational sampling two variants. Our findings reveal that protein maintains an overall resemblance terms site-specific glycan processing bond formation. Nonetheless, alterations glycans were observed at certain sites. These changes, synergy mutations within protein, result increased surface accessibility macromolecule, including ectodomain, receptor-binding domain, N-terminal domain. Additionally, mutagenesis pull-down assays role glycosylation a specific sequon (N149); furthermore, correlation MD simulation HDX-MS identified several high-dynamic areas proteins. insights contribute our understanding interplay between structure function, thereby advancing effective vaccination therapeutic strategies.

Language: Английский

Citations

2
Viral entry mechanisms: the role of molecular simulation in unlocking a key step in viral infections DOI Creative Commons
Mariana Valério, Carolina C. Buga, Manuel N. Melo

et al.

FEBS Open Bio, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Viral infections are a major global health concern, affecting millions of people each year. entry is one the crucial stages in infection process, but its details remain elusive. Enveloped viruses enclosed by lipid membrane that protects their genetic material and these linked to various human illnesses, including influenza, COVID‐19. Due advancements made field molecular simulation, significant progress has been unraveling dynamic processes involved viral enveloped viruses. Simulation studies have provided deep insight into function proteins responsible for attaching host receptors promoting fusion (fusion proteins), deciphering interactions between receptors, shedding light on functional significance key regions, such as peptide. These already significantly contributed our understanding this critical aspect assisted development effective strategies combat diseases improve health. This review focuses vital role facilitating process highlights contributions simulation uncover underlying mechanisms action.

Language: Английский

Citations

2
Mechanistic study of the transmission pattern of the SARS‐CoV‐2 omicron variant DOI Creative Commons
Ke An,

Xianzhi Yang,

Mengqi Luo

et al.

Proteins Structure Function and Bioinformatics, Journal Year: 2024, Volume and Issue: 92(6), P. 705 - 719

Published: Jan. 5, 2024

Abstract The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) characterized by 30 mutations in its spike protein, has rapidly spread worldwide since November 2021, significantly exacerbating the ongoing COVID‐19 pandemic. In order to investigate relationship between these and variant's high transmissibility, we conducted a systematic analysis mutational effect on spike–angiotensin‐converting enzyme‐2 (ACE2) interactions explored structural/energy correlation key mutations, utilizing reliable coarse‐grained model. Our study extended beyond receptor‐binding domain (RBD) trimer through comprehensive modeling full‐length rather than just RBD. free‐energy calculation revealed that enhanced binding affinity protein ACE2 receptor is correlated with increased structural stability isolated thus explaining heightened transmissibility. conclusion was supported our experimental analyses involving expression purification trimer. Furthermore, energy decomposition established those electrostatic make major contributions this effect. We categorized into four groups an analytical framework can be employed studying future mutations. Additionally, calculations rationalized reduced towards most available therapeutic neutralizing antibodies, when compared wild type. By providing concrete data offering solid explanation, contributes better understanding theories observations lays foundation for investigations.

Language: Английский

Citations

1
Impact of glycosylation on viral vaccines DOI

Antonio Lembo,

Antonio Molinaro, Cristina De Castro

et al.

Carbohydrate Polymers, Journal Year: 2024, Volume and Issue: 342, P. 122402 - 122402

Published: June 16, 2024

Language: Английский

Citations

1
Subtle changes at the RBD/hACE2 interface during SARS-CoV2 variant evolution: a molecular dynamics study DOI Creative Commons
Aria Gheeraert, Vincent Leroux, Dominique Mias‐Lucquin

et al.

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

Published: Dec. 13, 2024

The SARS-CoV-2 Omicron variants present a different behavior compared to the previous variants, all particularly in respect Delta variant, as it seems promote lower morbidity although being much more contagious. In this perspective, we performed new molecular dynamics (MD) simulations of various spike RBD/hACE2 complexes corresponding WT, and (BA.1 up BA.4/5) over 1.5 μs timescale. Then, carrying out comprehensive analysis residue interactions within between two partners, allowed us draw profile each variant by using complementary methods (PairInt, hydrophobic potential, contact PCA). Main results PairInt calculations highlighted most involved residues electrostatic that represent strong contribution binding with highly stable contacts RBD hACE2 (importance mutated at positions 417, 493 498). addition swappable arginine (493/498), apolar made substantial detection patches, one which was correlated energetic calculations. This study brings highlights on global resulting from networks cross-correlation matrices able detect subtle changes point mutations. our are also consistent alternative approaches such free energy but informative sensitive transient or low-energy interactions. Nevertheless, contributions 501 505 were good agreement measurements. PCA could identify intramolecular incidence S375F mutation occurring likely conferring them an advantage stability. Collectively, these data revealed major differences observed WT/Delta interface, may explain greater persistence Omicron.

Language: Английский

Citations

0
Impact of mutations on the plant-based production of recombinant SARS-CoV-2 RBDs DOI Creative Commons
Valentina Ruocco,

Ulrike Vavra,

Julia König-Beihammer

et al.

Frontiers in Plant Science, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 6, 2023

Subunit vaccines based on recombinant viral antigens are valuable interventions to fight existing and evolving viruses can be produced at large-scale in plant-based expression systems. The often derived from glycosylated envelope proteins of the virus glycosylation plays an important role for immunogenicity by shielding protein epitopes. receptor-binding domain (RBD) SARS-CoV-2 spike is a principal target vaccine development has been plants, but yields RBD variants were low N-glycosylation different concern less studied. Here, we investigated six transiently expressed leaves Nicotiana benthamiana. All purified functional terms receptor binding displayed almost full N-glycan occupancy both sites with predominately complex N-glycans. Despite high structural sequence conservation variants, detected variation yield which attributed lower differences unintentional proteolytic processing C-terminal polyhistidine tag used purification. Glycoengineering towards human-type profile core α1,6-fucose, showed that reactivity neutralizing antibody S309 differs depending variant.

Language: Английский

Citations

1
Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile DOI Open Access
Dongxia Wang, Zijian Zhang,

Jakub Baudys

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 23, 2023

Abstract SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics disulfide bonding of recombinant derived from Omicron variant (B.1.1.529) in comparison with D614G variant. Furthermore, conducted microsecond-long molecular dynamics simulations on resolve how different N-glycans impact conformational sampling two variants. Our findings reveal that protein maintains an overall resemblance terms site-specific glycan processing bond formation. Nonetheless, alterations glycans were observed at certain sites. These changes, synergy mutations within protein, result increased surface accessibility macromolecule, including ectodomain, receptor-binding domain, N-terminal domain. insights contribute our understanding interplay between structure function, thereby advancing effective vaccination therapeutic strategies. Teaser Through spectrometry simulations, is found be less covered by when compared

Language: Английский

Citations

1