Genetic features of SARS-CoV-2 Alpha, Delta, and Omicron variants and their association with the clinical severity of COVID-19 in Vietnam

IJID Regions, Journal Year: 2024, Volume and Issue: 11, P. 100348 - 100348

Published: March 13, 2024

We investigated genetic variations in the alpha, delta, and omicron variants of SARS-CoV-2 their association with clinical status treatment outcomes patients coronavirus disease 2019 (COVID-19). MiSeq was used to sequence genomes, MEGA 6.6 define nucleotide variations. determined between severity for variants. BA.1.1 BA.2 lineages variant had 57-59 mutations, which is 2-2.7-fold higher than that B.1.1.7 (alpha), B.1.617.2, AY.57 (delta) lineages. found distinct mutations SARS-CoV-2: 5 alpha (C26305T, G26558T, G7042T, C14120T, C27509T); 7 delta (C26408T, C1403T, C5184T, C9891T, T11418C, C11514T, C22227T); 3 C8991T, C25810T). Patients a severe rate 23.8%, critical 53.7%, mortality 38.9%, were significantly those The this study diversity differed from strains reported other countries, producing more

Language: Английский

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Impact of Missense Mutations on Spike Protein Stability and Binding Affinity in the Omicron Variant

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1150 - 1150

Published: July 17, 2024

The global effort to combat the COVID-19 pandemic faces ongoing uncertainty with emergence of Variants Concern featuring numerous mutations on Spike (S) protein. In particular, Omicron Variant is distinguished by 32 mutations, including 10 within its receptor-binding domain (RBD). These significantly impact viral infectivity and efficacy vaccines antibodies currently in use for therapeutic purposes. our study, we employed structure-based computational saturation mutagenesis approaches predict effects missense RBD stability binding affinity, comparing them original Wuhan-Hu-1 strain. Our results that such as G431W P507W induce most substantial destabilizations Wuhan-Hu-1-S/Omicron-S RBD. Notably, postulate Omicron-S exhibit a higher percentage enhancing affinity compared Wuhan-S. We found at residue positions G447, Y449, F456, F486, S496 led significant changes affinity. summary, findings may shed light widespread prevalence human populations. potentially enhance their receptors facilitate increased internalization infected cells, thereby infectivity. This informs development new neutralizing capable targeting Omicron's immune-evading aiding battle against pandemic.

Language: Английский

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Dynamics of Different Classes and Subclasses of Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Variants after Coronavirus Disease 2019 and CoronaVac Vaccination in Thailand

mSphere, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 23, 2023

The antibody responses to new SARS-CoV-2 variants that occur in different populations remain unclear. In this study, we recruited 60 participants, including COVID-19 patients and CoronaVac-vaccinated individuals, Thailand determined the dynamic levels of IgG, IgA, IgM, IgG subclasses antibodies against spike protein (S) four strains.

Language: Английский

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Emergence of Genomic Diversity in the Spike Protein of the “Omicron” Variant

Viruses, Journal Year: 2023, Volume and Issue: 15(10), P. 2132 - 2132

Published: Oct. 21, 2023

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus) has constantly been evolving into different forms throughout its spread in the population. Emerging variants, predominantly variants of concern (VOCs), could have an impact on virus spread, pathogenicity, and diagnosis. The recently emerged “Omicron” variant exhibited rapid transmission divergence. spike protein consistently appearing as mutational hotspot all these VOCs. In order to determine a deeper understanding extremely divergent “Omicron”, study amino acid usage patterns their substitution was performed compared with those other four successful (“Alpha”, “Beta”, “Gamma”, “Delta”). We observed that distinct pattern distinguishes it from VOCs is significantly correlated increased hydrophobicity proteins. increase non-synonymous rate Considering phylogenetic relationship, we hypothesized about functional interdependence between recombination mutation might resulted shift optimum for evolution variant. results suggest improved disease prevention control, more attention should be given significant genetic differentiation diversity newly emerging variants.

Language: Английский

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tANCHOR-cell-based assay for monitoring of SARS-CoV-2 neutralizing antibodies rapidly adaptive to various receptor-binding domains

iScience, Journal Year: 2024, Volume and Issue: 27(3), P. 109123 - 109123

Published: Feb. 5, 2024

Conventional neutralizing enzyme-linked immunosorbent assay (ELISA) systems for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimic the protein-protein interaction between angiotensin-converting enzyme (ACE2) and receptor-binding domain (RBD). However, an easy rapidly adaptative ELISA-based system testing antibodies against upcoming SARS-CoV-2 variants is urgently needed. In this study, we closed gap by developing a tANCHOR-cell-based RBD neutralization that avoids time-consuming protein expression purification followed coating on ELISA plates. This cell-based can be adopted to monitor (NAbs) variants. We show results obtained with strongly correlate commercially available surrogate assays NAbs. Moreover, technique directly measure binding cell-surface-exposed RBDs soluble ACE2. With technique, degree of antibody escape elicited emerging in current vaccination regimens determined reliably.

Language: Английский

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Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(6), P. e1012215 - e1012215

Published: June 10, 2024

New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, sublineage-defining vary between VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for at each position or stochastic nature their appearance. Here we show that lineages have distinct evolutionary spaces (a probabilistic definition sequence states can be occupied by expanding virus subpopulations). This space accurately inferred from patterns amino acid variability whole-protein level. Robust networks co-variable sites identify highest-likelihood new VOC and predict remarkably well emergence subvariants resistance to COVID-19 therapeutics. Our studies reveal contribution low frequency variant heterologous across protein accurate prediction changes interest.

Language: Английский

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Influence of Mutations on Physicochemical Properties of Spike Proteins from Prototypical SARS-CoV-2 Variants of Concern Detected in Amazonian Countries

Microbiology Research, Journal Year: 2024, Volume and Issue: 15(3), P. 1334 - 1345

Published: July 27, 2024

Since the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), viral spike protein (S) has become a target to describe appropriate epitopes for vaccine development and carry out epidemiological surveillance, especially regarding variants concern (VOCs). This study aimed evaluate influence mutations on physicochemical properties S proteins from prototypical SARS-CoV-2 VOCs detected in Amazonian countries. Using multiple computational tools, seven (B.1.1.7/P.1/B.1.617.2/BA.1/BA.2/BA.4/BA.5) were identified compared ancestral lineage virus (B). In all variants, most amino acids nonpolar; among polar acids, B.1.617.2/BA.1/BA.2/BA.4/BA.5 presented slightly higher proportion basic residues lower neutral residues. Unlike B.1.1.7/P.1/B.1.617.2, BA.1/BA.2 had greater content secondary structures, such as α-helices β-sheets. Regarding post-translational modifications, BA.2/BA.4/BA.5 fewer glycosylations phosphorylations. Finally, more prominent antigenic propensity N-terminal domain receptor-binding B.1.617.2/BA.4/BA.5 was observed. conclusion, omicron sequence variability other VOCs, influencing structural aspects that can potentially modulate its interaction with cellular receptors recognition by immune system.

Language: Английский

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The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 1787 - 1787

Published: July 25, 2022

The main protease (Mpro) of SARS-CoV-2 is an appealing target for the development antiviral compounds, due to its critical role in viral life cycle and high conservation among different coronaviruses continuously emerging mutants SARS-CoV-2. Ferulic acid (FA) a phytochemical with several health benefits that abundant plant biomass has been used as basis enzymatic or chemical synthesis derivatives improved properties, including activity against range viruses. This study tested 54 reported FA their inhibitory potential Mpro by silico simulations. Molecular docking was performed using Autodock Vina, resulting comparable better binding affinities 14 compounds compared known inhibitors N3 GC376. ADMET analysis showed limited bioavailability but significantly solubility enzymatically synthesized hits while druglikeness properties higher toxicity were observed chemically ones. MD simulations confirmed stability complexes most promising Mpro, highlighting rutinoside compound e27 best candidates from each derivative category.

Language: Английский

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SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 2, 2022

Abstract Since the emergence of SARS-CoV-2, five different variants concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Due to confounding factors in human population, such as pre-existing immunity, comparing severity disease caused by VOCs is challenging. Here, we investigate progression rhesus macaque model upon inoculation with Omicron BA.1, BA.2 VOCs. Disease macaques inoculated BA.1 or was lower than those Delta resulted significantly viral loads nasal swabs, bronchial cytology brush samples, lung tissue macaques. Cytokines chemokines were upregulated nasosorption samples animals compared animals. Overall, these data suggests that macaques, replicates levels VOC, resulting reduced clinical disease.

Language: Английский

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Utilization of Recombinant Baculovirus Expression System to Produce the RBD Domain of SARS-CoV-2 Spike Protein

Pathogens, Journal Year: 2022, Volume and Issue: 11(6), P. 672 - 672

Published: June 10, 2022

Continuous outbreaks of viral diseases in humans facilitates a need for the rapid development test kits and vaccines. These require expression systems to produce pure high yield target proteins. We utilized baculovirus-silkworm system receptor binding domain (RBD) SARS-CoV-2 spike protein. First, we had develop strategy constructing recombinant baculovirus RBD expression. For this, coding region

Language: Английский

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