The effects of amino acid substitution of spike protein and genomic recombination on the evolution of SARS-CoV-2

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 25, 2023

Over three years’ pandemic of 2019 novel coronavirus disease (COVID-19), multiple variants and subvariants have emerged successively, outcompeted earlier become predominant. The sequential emergence reflects the evolutionary process mutation-selection-adaption severe acute respiratory syndrome 2 (SARS-CoV-2). Amino acid substitution/insertion/deletion in spike protein causes altered viral antigenicity, transmissibility, pathogenicity SARS-CoV-2. Early pandemic, D614G mutation conferred virus with advantages over previous increased it also laid a conservative background for subsequent substantial mutations. role genomic recombination evolution SARS-CoV-2 raised increasing concern occurrence recombinants such as Deltacron, XBB.1.5, XBB.1.9.1, XBB.1.16 late phase pandemic. Co-circulation different co-infection immunocompromised patients accelerate recombinants. Surveillance variations, particularly recombination, is essential to identify ongoing changes genome antigenic epitopes thus leads development new vaccine strategies interventions.

Language: Английский

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Comparative Analysis of Conformational Dynamics and Systematic Characterization of Cryptic Pockets in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 Spike Complexes with the ACE2 Host Receptor: Confluence of Binding and Structural Plasticity in Mediating Networks of Conserved Allosteric Sites

Viruses, Journal Year: 2023, Volume and Issue: 15(10), P. 2073 - 2073

Published: Oct. 10, 2023

In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning cryptic pocket detection in a comparative examination of conformational landscapes systematic characterization allosteric sites SARS-CoV-2 Omicron BA.2, BA.2.75 XBB.1 spike full-length trimer complexes host receptor ACE2. Microsecond simulations, Markov state models mutational energies BA.2 domain revealed increased thermodynamic stabilization variant significant dynamic differences between these variants. Molecular ACE2 complemented studies enabled an in-depth analysis effects on functional adaptability Despite considerable structural similarities, variants can induce unique signatures specific distributions states. Using ensembles ACE2, conducted comprehensive screening to examine role mutations distribution mechanisms emerging sites. This captured all experimentally known discovered networks inter-connected functionally relevant that are governed by variant-sensitive structures. The results detailed how modulate conserved druggable pockets harboring important regions. for understanding roles be used allostery-mediated therapeutic intervention targeting states

Language: Английский

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Coarse-Grained Molecular Simulations and Ensemble-Based Mutational Profiling of Protein Stability in the Different Functional Forms of the SARS-CoV-2 Spike Trimers: Balancing Stability and Adaptability in BA.1, BA.2 and BA.2.75 Variants

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6642 - 6642

Published: April 2, 2023

Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, allosteric modulation. In this study, we embarked on a systematic comparative analysis dynamics, electrostatics, allostery in different states spike trimers for BA.1, BA.2, BA.2.75 variants. Using efficient accurate coarse-grained simulations atomistic reconstruction ensembles, examined dynamics agree with recent studies, suggesting are most stable among these A mutational scanning inter-protomer interfaces revealed group conserved structural stability hotspots play key role modulation also involved couplings through local contacts interaction networks sites. The results provided evidence more than BA.2 comparable to BA.1 variant. dynamic network modeling S trimers, showed mediators interactions associated major interconnected along potential communication pathways. increased thermodynamic variant may linked organization modularity residue allows communications between This study plausible rationale mechanism which mutations evolve targeting vulnerable sites adaptability elicit escape while maintaining their control balancing robust hotspots.

Language: Английский

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Coarse-Grained Molecular Simulations and Ensemble-Based Mutational Profiling of Protein Stability in the Different Functional Forms of the SARS-CoV-2 Spike Trimers : Balancing Stability and Adaptability in BA.1, BA.2 and BA.2.75 Variants

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 1, 2023

Abstract The evolutionary and functional studies suggested that the emergence of Omicron variants can be determined by multiple fitness trade-offs including immune escape, binding affinity, conformational plasticity, protein stability allosteric modulation. In this study, we embarked on a systematic comparative analysis dynamics, electrostatics, allostery in different states spike trimers for BA.1, BA.2, BA.2.75 variants. Using efficient accurate coarse-grained simulations atomistic reconstruction ensembles, examined dynamics agrees with recent studies, suggesting are most stable among these A mutational scanning inter-protomer interfaces revealed group conserved structural hotspots play key role modulation also involved couplings through local contacts interaction networks sites. results provided evidence more than BA.2 comparable to BA.1 variant. dynamic network modeling S showed positions driving long-range signaling associated major inter-connected along potential communication pathways, while sites mutations may often correspond weak spots but coupled networks. presented thermodynamic intimately linked residue organization allows broad ensemble communications which between modulated findings plausible rationale mechanisms evolve balance adaptability order ensure proper tradeoff stability, escape.

Language: Английский

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Current Progress in Genomic and Genetic Research on Human Viral Diseases

Frontiers research topics, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

it is a pioneering approach to the world of academia, radically improving way scholarly research managed.The grand vision Frontiers where all people have an equal opportunity seek, share and generate knowledge.Frontiers provides immediate permanent online open access its publications, but this alone not enough realize our goals. journal seriesThe series multi-tier interdisciplinary set openaccess, journals, promising paradigm shift from current review, selection dissemination processes in academic publishing.All journals are driven by researchers for researchers; therefore, they constitute service community.At same time, operates on revolutionary invention, tiered publishing system, initially addressing specific communities scholars, gradually climbing up broader public understanding, thus serving interests lay society, too. Dedication qualityEach article landmark highest quality, thanks genuinely collaborative interactions between authors review editors, who include some world's best academicians.Research must be certified peers before entering stream knowledge that may eventually reach -and shape society; only applies most rigorous unbiased reviews.Frontiers revolutionizes freely delivering outstanding research, evaluated with no bias both social point view.By applying advanced information technologies, catapulting into new generation.

Language: Английский

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Respiratory Pathogen Coinfection During Intersecting COVID-19 and Influenza Epidemics

Pathogens, Journal Year: 2024, Volume and Issue: 13(12), P. 1113 - 1113

Published: Dec. 17, 2024

Respiratory pathogen coinfections pose significant challenges to global public health, particularly regarding the intersecting epidemics of COVID-19 and influenza. This study investigated incidences respiratory infectious pathogens in this unique context. We collected throat swab samples from 308 patients with a fever outpatient emergency departments at sentinel surveillance hospitals Xiamen, southeast China, between April May 2023, testing for SARS-CoV-2 26 other pathogens. The coinfection rate XBB variant was higher than that observed during Alpha Delta phases. Among influenza, bacterial were more prevalent. Only 0.65% (2/308) concurrently infected both Age-stratified analysis showed clear pattern, incidence children under 18 years age. These findings highlight need timely detection implementation appropriate interventions, crucial reducing disease burden epidemics.

Language: Английский

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Serum neutralization of SARS-CoV-2 Omicron BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1 and XBB.1.5 in individuals receiving Evusheld

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: March 23, 2023

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is undergoing continuous evolution and convergent mutation, which has led to the rapid emergence of several new variants. These subvariants carry different mutations in theirreceptor-binding domain (RBD), raising concerns that they may evade neutralizing monoclonal antibodies (mAbs). In this study, we investigated serum neutralization efficacy Evusheld (cilgavimab tixagevimab) antibody cocktails against SARS-CoV-2 sublineages BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1 XBB.1.5. Our results show retained activity BA.2.75 albeit with somewhat reduced titers. However, XBB.1.5 significantly decreased, showing greatest escape among subvariants, followed by BQ.1.1, BA.2.76 BF.7. We also observed recipients displayed elevated levels their serum, efficiently neutralized original variant, exhibited characteristics infection than those who did not receive Evusheld. findings provide important guidance for application treating subvariant infections.

Language: Английский

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Examining Functional Linkages Between Conformational Dynamics, Protein Stability and Evolution of Cryptic Binding Pockets in the SARS-CoV-2 Omicron Spike Complexes with the ACE2 Host Receptor: Recombinant Omicron Variants Mediate Variability of Conserved Allosteric Sites and Binding Epitopes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 12, 2023

Abstract In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning cryptic pocket detection in a comparative examination of conformational landscapes systematic characterization allosteric sites SARS-CoV-2 Omicron BA.2, BA.2.75 XBB.1 spike full-length trimer complexes host receptor ACE2. Microsecond simulations, Markov state models mutational energies BA.2 domain revealed increased thermodynamic stabilization variant significant dynamic differences between these variants. Molecular full length ACE2 complemented studies enabled an in-depth analysis effects on functional adaptability Despite considerable structural similarities, variants can induce unique signatures specific distributions states. Using ensembles ACE2, conducted comprehensive screening to examine role mutations distribution mechanisms emerging sites. This captured all experimentally known discovered networks inter-connected functionally relevant that are governed by variant-sensitive structures. The results detailed how modulate conserved druggable pockets harboring important regions. for understanding roles be used allostery-mediated therapeutic intervention targeting states

Language: Английский

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