Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

Environmental Research, Год журнала: 2022, Номер 209, С. 112816 - 112816

Опубликована: Янв. 29, 2022

Язык: Английский

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Charge Matters: Mutations in Omicron Variant Favor Binding to Cells

ChemBioChem, Год журнала: 2022, Номер 23(6)

Опубликована: Янв. 12, 2022

Abstract Evidence is strengthening to suggest that the novel SARS‐CoV‐2 mutant Omicron, with its more than 60 mutations, will spread and dominate worldwide. Although mutations in spike protein are known, molecular basis for why additional have not previously occurred account Omicron's higher infection potential, understood. We propose, based on chemical rational dynamics simulations, elevated occurrence of positively charged amino acids certain domains (Delta: +4; Omicron: +5 vs. wild type) increases binding cellular polyanionic receptors, such as heparan sulfate due multivalent charge‐charge interactions. This observation a starting point targeted drug development.

Язык: Английский

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Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant

Journal of Medical Virology, Год журнала: 2022, Номер 94(5), С. 1876 - 1885

Опубликована: Янв. 27, 2022

COVID's Omicron variant has sparked a slew of concerns across the globe. This review aims to provide brief overview what we know about right now. The new been discovered in 149 countries all six World Health Organization (WHO) regions since its discovery South Africa on November 24, 2021 and became dominant country less than 3 weeks. WHO warned that B.1.1.529 is spreading at an unprecedented rate, urged prepare for worst. Over course this time, researchers from around world have uncovered wealth information virus's epidemiology biological properties. Case numbers are increasing exponentially hard-hit areas such as Africa, United Kingdom, USA (overtaking delta variant), implying highly transmissible. Initial research provided some insights into efficacy vaccines against whether it produces major illness, however, much remains unknown, additional work needed investigate initial reports represent real-world situations.

Язык: Английский

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Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 30, 2024

Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue spread. Here, we show exhibits increased infectivity in primary adult upper airway tissue relative Delta. Using recombinant forms nasal epithelial cells cultured at the liquid-air interface, mutations unique Spike enable enhanced entry into tissue. Unlike earlier SARS-CoV-2, our findings suggest enters independently serine transmembrane proteases instead relies upon metalloproteinases catalyze membrane fusion. Furthermore, demonstrate this pathway unlocked by enables evasion from constitutive interferon-induced antiviral factors restrict attachment. Therefore, transmissibility exhibited humans may be attributed not only its vaccine-elicited adaptive immunity, but also superior invasion epithelia resistance cell-intrinsic barriers present therein.

Язык: Английский

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SARS-CoV-2 evolved variants optimize binding to cellular glycocalyx

Cell Reports Physical Science, Год журнала: 2023, Номер 4(4), С. 101346 - 101346

Опубликована: Апрель 1, 2023

Viral variants of concern continue to arise for SARS-CoV-2, potentially impacting both methods detection and mechanisms action. Here, we investigate the effect an evolving spike positive charge in SARS-CoV-2 subsequent interactions with heparan sulfate angiotensin converting enzyme 2 (ACE2) glycocalyx. We show that positively charged Omicron variant evolved enhanced binding rates negatively Moreover, discover while spike-ACE2 affinity is comparable Delta variant, are significantly enhanced, giving rise a ternary complex spike-heparan sulfate-ACE2 large proportion double-bound triple-bound ACE2. Our findings suggest evolve be more dependent on viral attachment infection. This discovery enables us engineer second-generation lateral-flow test strip harnesses heparin ACE2 reliably detect all concern, including Omicron.

Язык: Английский

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Antiviral fibrils of self-assembled peptides with tunable compositions

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 7, 2024

The lasting threat of viral pandemics necessitates the development tailorable first-response antivirals with specific but adaptive architectures for treatment novel infections. Here, such an antiviral platform has been developed based on a mixture hetero-peptides self-assembled into functionalized β-sheets capable multivalent binding to protein complexes. One domain each hetero-peptide is designed specifically bind certain proteins, while another self-assembles fibrils epitope characteristics determined by types peptides and their molar fractions. maintain enhanced complexes retain high resilience mutations. This method experimentally computationally tested using short that Spike proteins SARS-CoV-2. efficacious, inexpensive, stable excellent tolerability.

Язык: 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, Год журнала: 2024, Номер 64(4), С. 1407 - 1418

Опубликована: Фев. 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.

Язык: Английский

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Balancing stability and function: impact of the surface charge of SARS-CoV-2 Omicron spike protein

npj Viruses, Год журнала: 2025, Номер 3(1)

Опубликована: Апрель 1, 2025

Abstract The ectodomain of the Omicron SARS-CoV-2 spike has an increased positive surface charge, favoring binding to host cell surface, but may affect stability ectodomain. Thermal studies identified two transitions associated with flexibility receptor domain and unfolding whole ectodomain, respectively. Despite destabilizing effects some mutations, compensatory mutations maintain ECD functional advantages thus supporting viral fitness.

Язык: Английский

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Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule

The Journal of Physical Chemistry B, Год журнала: 2022, Номер 126(36), С. 6835 - 6852

Опубликована: Сен. 6, 2022

Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved interaction receptor-binding domain (RBD) SARS-CoV-2 spike protein with human receptor Angiotensin-converting enzyme 2 (ACE2). As principal computational tool, we used FORTE approach, capable to model proton fluctuations and computing free energies for a very large number protein–protein systems under different physical–chemical conditions, here focusing on RBD-ACE2 interactions. Both wild-type all critical variants included this study. From our ensemble extensive simulations, obtain, as function pH, binding affinities, charges proteins, their charge regulation capacities, dipole moments. In addition, calculated pKas ionizable residues mapped coupling between them. able present simple predictor based data obtained Alpha, Beta, Gamma, Delta, Omicron variants, linear correlation total RBD corresponding affinity. This "RBD rule" should work quick test degree severity coming future.

Язык: Английский

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A fast, ultrasensitive SERS immunoassay to detect SARS-CoV-2 in saliva

Analytica Chimica Acta, Год журнала: 2022, Номер 1229, С. 340290 - 340290

Опубликована: Авг. 23, 2022

Язык: Английский

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