Evolution of increased positive charge on the SARS-CoV-2 spike protein may be adaptation to human transmission

iScience, Год журнала: 2023, Номер 26(3), С. 106230 - 106230

Опубликована: Фев. 18, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and infect individuals. exterior surface of the SARS-CoV-2 virion is dominated by spike protein, current work examined protein biochemical features that have changed during 3 years in which has infected humans. Our analysis identified a striking change charge, from −8.3 original Lineage A B viruses −1.26 most Omicron viruses. We conclude addition immune selection pressure, evolution also altered viral properties, may influence survival promote transmission. Future vaccine therapeutic development should exploit target these properties.

Язык: Английский

---

Omicron Coronavirus: pH-Dependent Electrostatic Potential and Energy of Association of Spike Protein to ACE2 Receptor

Viruses, Год журнала: 2023, Номер 15(8), С. 1752 - 1752

Опубликована: Авг. 17, 2023

The association of the S-protein SARS-CoV-2 beta coronavirus to ACE2 receptors human epithelial cells determines its contagiousness and pathogenicity. We computed pH-dependent electric potential on surface interacting globular proteins Gibbs free energy at wild-type strain omicron variant. calculated isoelectric points receptor (pI 5.4) in trimeric form 7.3, wild type), 7.8, variant), experimentally verified by focusing, show that pH 6-7, S1-ACE2 is conditioned electrostatic attraction oppositely charged viral protein. comparison local potentials variant shows point mutations alter a relatively small area receptor-binding domain (RBD) S1 subunit. appearance seven charge-changing RBD (equivalent three additional positive charges) leads stronger 5.5 (typical for respiratory tract) weaker one 7.4 (characteristic blood plasma); this reveals reason higher but lower pathogenicity strain.

Язык: Английский

---

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

Bioinformatics Advances, Год журнала: 2024, Номер 4(1)

Опубликована: Янв. 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.

Язык: Английский

---

Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

Macromolecules, Год журнала: 2022, Номер 55(18), С. 7957 - 7973

Опубликована: Сен. 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.

Язык: Английский

---

Functionalized Fullerene for Inhibition of SARS‐CoV‐2 Variants

Small, Год журнала: 2023, Номер 19(15)

Опубликована: Янв. 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.

Язык: Английский

---

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

Advanced Materials, Год журнала: 2024, Номер 36(32)

Опубликована: Май 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.

Язык: Английский

---

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

iScience, Год журнала: 2022, Номер 25(10), С. 105044 - 105044

Опубликована: Сен. 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.

Язык: Английский

---

Host Membranes as Drivers of Virus Evolution

Viruses, Год журнала: 2023, Номер 15(9), С. 1854 - 1854

Опубликована: Авг. 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.

Язык: Английский

---

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

---

Charge Regulation Triggers Condensation of Short Oligopeptides to Polyelectrolytes

JACS Au, Год журнала: 2024, Номер 4(5), С. 1775 - 1785

Опубликована: Март 13, 2024

Electrostatic interactions between charged macromolecules are ubiquitous in biological systems, and they important also materials design. Attraction oppositely molecules is often interpreted as if the had a fixed charge, which not affected by their interaction. Less commonly, charge regulation invoked to interpret such interactions, i.e., change of state response local environment. Although some theoretical simulation studies suggest that plays an role intermolecular experimental evidence supporting view very scarce. In current study, we used model system, composed long polyanion interacting with cationic oligolysines, containing up 8 lysine residues. We showed using both simulations experiments while these lysines only weakly absence polyanion, condense on polycations pH close pKa side chains. show coexist two distinct populations within same solution: (1) practically nonionized free solution; (2) highly ionized condensed polyanion. Using this demonstrate under what conditions significant generalize our findings beyond specific system here.

Язык: Английский

---