Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus DOI Open Access
S. Hristova, Alexandar M. Zhivkov

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2174 - 2174

Published: Feb. 11, 2024

The contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus–receptor electrostatic association its positively charged spike (S) protein with negatively angiotensin converting enzyme-2 (ACE2 receptor) epithelial cells. If some mutations occur, potential on surface receptor-binding domain (RBD) could be altered, and S-ACE2 become stronger or weaker. aim current research to investigate whether point can noticeably alter RBD 3D stability S1-subunit S-protein. For this purpose, 15 mutants different hydrophilicity electric charge (positive, negative, uncharged) substituted substituting amino acid residues, located at S1-ACE2 interface, are selected, structure reconstructed base crystallographic S-protein wild-type strain sequence unfolded polypeptide chain mutants. Then, Gibbs free energy folding, isoelectric point, pH-dependent computed using programs for electrostatics. results show alterations in local vicinity mutant residue, which influence association. This approach allows prediction relative infectivity, transmissibility, (at equal social immune status) new reconstruction calculation potential.

Language: Английский

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 DOI Open Access
Rekha Khandia, Shailja Singhal, Taha Alqahtani

et al.

Environmental Research, Journal Year: 2022, Volume and Issue: 209, P. 112816 - 112816

Published: Jan. 29, 2022

Language: Английский

Citations

283
Charge Matters: Mutations in Omicron Variant Favor Binding to Cells DOI Creative Commons
Chuanxiong Nie, Anil Kumar Sahoo, Roland R. Netz

et al.

ChemBioChem, Journal Year: 2022, Volume and Issue: 23(6)

Published: Jan. 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.

Language: Английский

Citations

82
Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant DOI
Vineet Sharma, Himanshu Rai, Dev Nath Singh Gautam

et al.

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(5), P. 1876 - 1885

Published: Jan. 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.

Language: Английский

Citations

79
Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue DOI Creative Commons

Guoli Shi,

Tiansheng Li, Kin Kui Lai

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 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.

Language: Английский

Citations

20
SARS-CoV-2 evolved variants optimize binding to cellular glycocalyx DOI Creative Commons
Sang Hoon Kim, Fiona L. Kearns, Mia A. Rosenfeld

et al.

Cell Reports Physical Science, Journal Year: 2023, Volume and Issue: 4(4), P. 101346 - 101346

Published: April 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.

Language: Английский

Citations

43
Antiviral fibrils of self-assembled peptides with tunable compositions DOI Creative Commons

Joseph Dodd‐o,

Abhishek Roy, Zain Siddiqui

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 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.

Language: Английский

Citations

12
Balancing stability and function: impact of the surface charge of SARS-CoV-2 Omicron spike protein DOI Creative Commons
Daniel Lauster, Rainer Haag, Matthias Ballauff

et al.

npj Viruses, Journal Year: 2025, Volume and Issue: 3(1)

Published: April 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.

Language: Английский

Citations

1
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 DOI
Fernando Luís Barroso da Silva, Carolina Corrêa Giron, Aatto Laaksonen

et al.

The Journal of Physical Chemistry B, Journal Year: 2022, Volume and Issue: 126(36), P. 6835 - 6852

Published: Sept. 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.

Language: Английский

Citations

33
A fast, ultrasensitive SERS immunoassay to detect SARS-CoV-2 in saliva DOI

Moein Mohammadi,

Delphine Antoine,

Madison Vitt

et al.

Analytica Chimica Acta, Journal Year: 2022, Volume and Issue: 1229, P. 340290 - 340290

Published: Aug. 23, 2022

Language: Английский

Citations

30
Evolution of increased positive charge on the SARS-CoV-2 spike protein may be adaptation to human transmission DOI Creative Commons
Matthew Cotten, My V. T. Phan

iScience, Journal Year: 2023, Volume and Issue: 26(3), P. 106230 - 106230

Published: Feb. 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.

Language: Английский

Citations

20