Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages

Bioinformatics Advances, Journal Year: 2024, Volume and Issue: 4(1)

Published: Jan. 1, 2024

Abstract Motivation Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding different cell surface receptors, non-specific electrostatic interactions with environment, and structural stability conformation. It is therefore important obtain a good understanding mutations that affect total charge which arisen across SARS-CoV-2 lineages during course virus’ evolution. Results We analyse change in number ionizable acids corresponding proteins almost 2200 emerged over span pandemic. Our results show previously observed trend toward an increase positive variants concern has essentially stopped emergence early omicron variants. Furthermore, recently greater diversity terms their composition acids. also demonstrate patterns are characteristic related within broader clade division phylogenetic tree. Due ubiquity biological our findings relevant for broad range studies dealing environment. Availability implementation The data underlying article available Supplementary material.

Language: Английский

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TransEFVP: A Two-Stage Approach for the Prediction of Human Pathogenic Variants Based on Protein Sequence Embedding Fusion

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(4), P. 1407 - 1418

Published: Feb. 9, 2024

Studying the effect of single amino acid variations (SAVs) on protein structure and function is integral to advancing our understanding molecular processes, evolutionary biology, disease mechanisms. Screening for deleterious variants one crucial issues in precision medicine. Here, we propose a novel computational approach, TransEFVP, based large-scale language model embeddings transformer-based neural network predict disease-associated SAVs. The adopts two-stage architecture: first stage designed fuse different feature through transformer encoder. In second stage, support vector machine employed quantify pathogenicity SAVs after dimensionality reduction. prediction performance TransEFVP blind test data achieves Matthews correlation coefficient 0.751, an F1-score 0.846, area under receiver operating characteristic curve 0.871, higher than existing state-of-the-art methods. benchmark results demonstrate that can be explored as accurate effective SAV method. codes are available at https://github.com/yzh9607/TransEFVP/tree/master academic use.

Language: Английский

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Mucus‐Inspired Self‐Healing Hydrogels: A Protective Barrier for Cells against Viral Infection

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(32)

Published: May 30, 2024

Mucus is a dynamic biological hydrogel, composed primarily of the glycoprotein mucin, exhibits unique biophysical properties and forms barrier protecting cells against broad-spectrum viruses. Here, this work develops polyglycerol sulfate-based dendronized mucin-inspired copolymer (MICP-1) with ≈10% repeating units activated disulfide as cross-linking sites. Cryo-electron microscopy (Cryo-EM) analysis MICP-1 reveals an elongated single-chain fiber morphology. shows potential inhibitory activity many viruses such herpes simplex virus 1 (HSV-1) SARS-CoV-2 (including variants Delta Omicron). produces hydrogels viscoelastic similar to healthy human sputum tuneable microstructures using linear branched polyethylene glycol-thiol (PEG-thiol) cross-linkers. Single particle tracking microrheology, electron paramagnetic resonance (EPR) cryo-scanning (Cryo-SEM) are used characterize network structures. The synthesized exhibit self-healing properties, along that through reduction. A transwell assay investigate hydrogel's protective viral infection HSV-1. Live-cell confirms these can protect underlying from by trapping virus, due both morphology anionic multivalent effects. Overall, novel generates mucus-mimetic on multi-gram scale. These be models for disulfide-rich airway mucus research, biomaterials.

Language: Английский

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Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

Macromolecules, Journal Year: 2022, Volume and Issue: 55(18), P. 7957 - 7973

Published: Sept. 11, 2022

Heparin (HP) and heparan sulfate (HS) are linear, anionically charged polysaccharides well-known for their diverse biological activities. While HP is generally localized in mast cells connective tissues, HS part of the glycocalyx involved attachment viruses to host cells, constituting first step an infection. also exhibit antiviral activity by blocking viral receptors, thereby inhibiting from engaging with cells. Inspired structural features, such as high molecular weight polyanionic character, various synthetic polymers mimicking HP/HS have been developed used model systems study bioactivity, well therapeutic applications. This Perspective provides overview roles engagement, examines historical recent approaches toward oligo-/polysaccharide, glycopolymer, anionic polymer mimetics. An current applications future prospects these molecules provided, demonstrating potential addressing epidemics pandemics.

Language: Английский

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Functionalized Fullerene for Inhibition of SARS‐CoV‐2 Variants

Small, Journal Year: 2023, Volume and Issue: 19(15)

Published: Jan. 18, 2023

Abstract As virus outbreaks continue to pose a challenge, nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading inhibition. Similarly, hydrophobic C 60 fullerene prevent infection via with cavities of surface proteins. Here, two strategies are combined inhibit SARS‐CoV‐2 variants in vitro. Effective inhibitory concentrations the millimolar range highlight significance bare fullerene's moiety electrostatic polysulfates proteins SARS‐CoV‐2. Furthermore, microscale thermophoresis measurements support linear polyglycerol interact its spike protein, importance within it. All‐atom molecular dynamics simulations reveal binding site is situated close receptor domain, 4 nm sulfate sites, feasibly allowing both portions material simultaneously.

Language: Английский

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Host Membranes as Drivers of Virus Evolution

Viruses, Journal Year: 2023, Volume and Issue: 15(9), P. 1854 - 1854

Published: Aug. 31, 2023

The molecular mechanisms controlling the adaptation of viruses to host cells are generally poorly documented. An essential issue resolve is whether membranes, and especially lipid rafts, which usually considered passive gateways for many enveloped viruses, also encode informational guidelines that could determine virus evolution. Due their enrichment in gangliosides confer an electronegative surface potential, rafts impose a first control level favoring selection with enhanced cationic areas, as illustrated by SARS-CoV-2 variants. Ganglioside clusters attract viral particles dynamic electrostatic funnel, more population winning race. However, forces account only small part energy raft-virus interaction, depends mainly on ability form network hydrogen bonds raft gangliosides. This fine tuning virus-ganglioside interactions, stabilize membrane, generates second pressure driven typical induced-fit mechanism. Gangliosides play active role this process, wrapping around spikes through quicksand-like Viruses thus endless race access they bound evolve perpetually, combining speed (electrostatic potential) precision (fine amino acids) under selective immune system. Deciphering membrane evolution may open new avenues design innovative antivirals.

Language: Английский

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Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics

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

Published: Jan. 10, 2024

Abstract The worldwide spread of SARS-CoV-2 has been characterised by the emergence several variants concern (VOCs) presenting an increasing number mutations in viral genome. spike glycoprotein, responsible for engaging receptor ACE2, exhibits highest density mutations, suggesting ongoing evolution to optimize entry. However, previous studies focussed on isolated molecular interactions, neglecting intricate composition plasma membrane and interplay between attachment factors. Our study explores role avidity complexity modulating virus-host binding kinetics during early stages entry original Wuhan strain three VOCs: Omicron BA.1, Delta, Alpha. We employ fluorescent liposomes decorated with from VOCs as virion mimics single-particle tracking native supported lipid bilayers derived pulmonary Calu-3 cells. findings reveal increase affinity multivalent bond cell surface driven increased association rate. show that heparan sulfate (HS), a sulfated glycosaminoglycan commonly expressed cells’ membrane, plays central interaction we observe shift its screening ACE2 important factor Omicron. This is caused ∼10-fold Omicron’s HS compared strain, shown using atomic force microscopy-based single-molecule spectroscopy. results importance coreceptors, particularly HS, modulation VOCs. highlight transition variants’ strategy towards use initial docking site, which likely shaping tropism infection upper airways, milder symptoms, higher transmissibility.

Language: Английский

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The mechanisms of immune response and evasion by the main SARS-CoV-2 variants

iScience, Journal Year: 2022, Volume and Issue: 25(10), P. 105044 - 105044

Published: Sept. 2, 2022

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a global pandemic. SARS-CoV-2 carries unique group of mutations, and the transmission virus led to emergence other mutants such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2) Omicron (B.1.1.529). The advent vaccine raised hopes ending However, mutation variants have concerns about effectiveness vaccines because data showed that was less effective against compared previous variants. Mutation could easily mutate N-segment structure receptor domain its spike glycoprotein (S) protein escape antibody recognition. Therefore, it is vital understand potential immune response evasion mechanism In this review, mechanisms several are described, which provide some helpful advice for future vaccines.

Language: Английский

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Molecular dynamics studies reveal structural and functional features of the SARS‐CoV‐2 spike protein

BioEssays, Journal Year: 2022, Volume and Issue: 44(9)

Published: July 17, 2022

Abstract The SARS‐CoV‐2 virus is responsible for the COVID‐19 pandemic world experience since 2019. protein first steps of cell invasion, spike protein, has probably received most attention in light its central role during infection. Computational approaches are among tools employed by scientific community enormous effort to study this new affliction. One these methods, namely molecular dynamics (MD), been used characterize function at atomic level and unveil structural features from a dynamic perspective. In review, we focus on main findings, including flexibility, rare S conformational changes, cryptic epitopes, glycans, drug repurposing, effect variants.

Language: Английский

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A study on the effect of natural products against the transmission of B.1.1.529 Omicron

Virology Journal, Journal Year: 2023, Volume and Issue: 20(1)

Published: Aug. 25, 2023

Abstract Background The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by World Health Organization. However, large population is still unvaccinated, leading to emergence mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from Organization raised concerns about Omicron variant, which emerged South Africa during surge COVID-19 cases November 2021. Vaccines are not proven completely effective or safe against Omicron, clinical trials for combating infection virus. absence suitable pharmaceuticals has led scientists clinicians search alternative supplementary therapies, including dietary patterns, reduce effect strains. Main body This review analyzed aetiology, epidemiology, natural products Omicron. Although literature did include keywords related silico computational research, investigations were emphasized this study. Molecular docking was implemented compare interaction between Chloroquine with ACE2 receptor protein amino acid residues global proceeding SARS-CoV-2 also elucidated. results suggest that DGCG may bind three times more effectively than standard chloroquine. Conclusion variant highlighted need therapies impact current suggests such as be binding however, further research required validate study explore potential mitigate COVID-19. Graphical abstract

Language: Английский

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