Increased preference for lysine over arginine in spike proteins of SARS-CoV-2 BA.2.86 variant and its daughter lineages DOI Creative Commons
Anže Božič, Rudolf Podgornik

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0320891 - e0320891

Published: April 7, 2025

The COVID-19 pandemic offered an unprecedented glimpse into the evolution of its causative virus, SARS-CoV-2. It has been estimated that since outbreak in late 2019, virus explored all possible alternatives terms missense mutations for sites polypeptide chain. Spike protein exhibits largest sequence variation particular, with many individual impacting target recognition, cellular entry, and endosomal escape virus. Moreover, recent studies unveiled a significant increase total charge on spike during initial period pandemic. While this trend recently come to halt, we perform sequence-based analysis 2665 SARS-CoV-2 variants which shows ionizable amino acids continue occur newly emerging variants, notable differences between lineages from different clades. What is more, show within can acquire positive charge, prominent preference lysine residues over arginine residues. This lysine-to-arginine ratio increased at several points evolution, most BA.2.86 sublineages, including dominant JN.1, KP.3, XEC variants. consequence structural regions now among highest viral species Coronaviridae family. impact high proteins daughter fitness remains unclear; discuss potential mechanisms could play role serve as starting point further studies.

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

282
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

78
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

19
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

41
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

32
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

29
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
Omicron Coronavirus: pH-Dependent Electrostatic Potential and Energy of Association of Spike Protein to ACE2 Receptor DOI Creative Commons
S. Hristova, Alexandar M. Zhivkov

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1752 - 1752

Published: Aug. 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.

Language: Английский

Citations

18
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

8