SARS-CoV-2 Omicron Subvariants Do Not Differ Much in Binding Affinity to Human ACE2: A Molecular Dynamics Study

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(14), P. 3340 - 3349

Published: April 2, 2024

The emergence of the variant concern Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exacerbates COVID-19 pandemic due to its high contagious ability. Studies have shown that binds human ACE2 more strongly than wild type. prevalence in new cases promotes novel lineages with improved receptor binding affinity and immune evasion. To shed light on this open problem, work, we investigated free energy domain BA.2, BA.2.3.20, BA.3, BA4/BA5, BA.2.75, BA.2.75.2, BA.4.6, XBB.1, XBB.1.5, BJ.1, BN.1, BQ.1.1, CH.1.1 using all-atom molecular dynamics simulation mechanics Poisson–Boltzmann surface area method. results show these increased compared BA.1 lineage, BA.2.75 BA.2.75.2 subvariants bind others. However, general, affinities do not differ significantly from each other. electrostatic force dominates over van der Waals interaction between cells. Based our results, argue viral evolution does further improve SARS-CoV-2 for but may increase

Language: Английский

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Antiviral activity of an ACE2-Fc fusion protein against SARS-CoV-2 and its variants

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0312402 - e0312402

Published: Jan. 3, 2025

SARS-CoV-2 has continued spreading around the world in recent years since initial outbreak 2019, frequently developing into new variants with greater human infectious capacity. and its mutants use angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor, which triggered several therapeutic strategies against COVID-19 relying on of ACE2 recombinant proteins decoy receptors. In this work, we propose an silent Fc fusion protein (ACE2-hFcLALA) candidate therapy COVID-19. This was able to block binding RBD receptor measured by ELISA flow cytometry inhibition assays. Moreover, used classical neutralization assays progeny assay show that ACE2-hFcLALA is capable neutralizing authentic virus. Additionally, found more effective preventing vitro infection different interest ( alpha , beta delta omicron ) compared D614G strain. Our results suggest potential molecule be both preventive settings current emerging gateway cells.

Language: Английский

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Exigency of Plant-Based Vaccine against COVID-19 Emergence as Pandemic Preparedness

Vaccines, Journal Year: 2023, Volume and Issue: 11(8), P. 1347 - 1347

Published: Aug. 9, 2023

After two years since the declaration of COVID-19 as a pandemic by World Health Organization (WHO), more than six million deaths have occurred due to SARS-CoV-2, leading an unprecedented disruption global economy. Fortunately, within year, wide range vaccines, including pathogen-based inactivated and live-attenuated replicating non-replicating vector-based nucleic acid (DNA mRNA)-based protein-based subunit virus-like particle (VLP)-based been developed mitigate severe impacts pandemic. These vaccines proven highly effective in reducing severity illness preventing deaths. However, availability supply become issue prioritization vaccine distribution most countries. Additionally, virus continues mutate spread, questions arisen regarding effectiveness against new strains SARS-CoV-2 that can evade host immunity. The urgent need for booster doses enhance immunity has recognized. scarcity “safe effective” exacerbated inequalities terms coverage. development fallen short expectations set forth 2020 2021. Furthermore, equitable at national levels remains challenge, particularly developing In such circumstances, exigency plant virus-based apparent means overcome shortages through fast manufacturing processes enable quick convenient millions people without reliance on cold chain system. Moreover, demonstrated both safety efficacy eliciting robust cellular immunogenicity pathogens. This review aims shed light advantages disadvantages different types provide update current status plant-based fight

Language: Английский

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Efficient discovery of frequently co-occurring mutations in a sequence database with matrix factorization

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(4), P. e1012391 - e1012391

Published: April 24, 2025

We have developed a robust method for efficiently tracking multiple co-occurring mutations in sequence database. Evolution often hinges on the interaction of several to produce significant phenotypic changes that lead proliferation variant. However, identifying numerous simultaneous across vast database sequences poses computational challenge. Our approach leverages matrix factorization technique automatically and pinpoint subsets positions where co-mutations occur, appearing substantial number within validated our using SARS-CoV-2 receptor-binding domains, comprising approximately seven hundred thousand Spike protein, demonstrating superior performance compared reasonably exhaustive brute-force method. Furthermore, we explore biological significance identified co-mutational (CMPs) their potential impact virus’s evolution functionality, key Delta Omicron variants. This analysis underscores role CMPs understanding evolutionary trajectory. By “birth" “death" CMPs, can elucidate persistence specific groups different viral strains, providing valuable insights into virus’ adaptability thus, possibly aiding vaccine design strategies.

Language: Английский

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Detection and Characterisation of SARS-CoV-2 in Eastern Province of Zambia: A Retrospective Genomic Surveillance Study

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6338 - 6338

Published: June 7, 2024

Mutations have driven the evolution and development of new variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for increased transmissibility, disease severity vaccine escape among others. Genome sequencing is a technique that allows scientists to read genetic code an organism has become powerful tool studying emerging infectious diseases. Here, we conducted cross-sectional study in selected districts Eastern Province Zambia, from November 2021 February 2022. We analyzed SARS-CoV-2 samples (n = 76) using high-throughput sequencing. A total 4097 mutations were identified 69 genomes 47% (1925/4097) occurring spike protein. 83 unique amino acid protein seven Omicron sublineages (BA.1, BA.1.1, BA.1.14, BA.1.18, BA.1.21, BA.2, BA.2.23 XT). Of these, 43.4% (36/83) present receptor binding domain, while 14.5% (12/83) motif. While recombinant XT strain, highly transmissible BA.2 sublineage was more predominant (40.8%). observed substitution other strain Province. This work shows importance pandemic preparedness need monitor general population.

Language: Английский

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Analysis the molecular similarity of least common amino acid sites in ACE2 receptor to predict the potential susceptible species for SARS-CoV-2

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(5), P. e0293441 - e0293441

Published: May 2, 2024

SARS-CoV-2 infections in animals have been reported globally. However, the understanding of complete spectrum susceptible to remains limited. The virus’s dynamic nature and its potential infect a wide range are crucial considerations for One Health approach that integrates both human animal health. This study introduces bioinformatic predict susceptibility domestic wild animals. By examining genomic sequencing, we establish phylogenetic relationships between virus hosts. We focus on interaction genome sequence specific regions host species’ ACE2 receptor. analyzed compared receptor sequences from 29 species known be infected, selecting 10 least common amino acid sites (LCAS) key binding domains based similarity patterns. Our analysis included 49 across primates, carnivores, rodents, artiodactyls, revealing consistency LCAS identifying them as potentially susceptible. employed pattern likelihood infection unexamined species. method serves valuable screening tool assessing risks animals, aiding prevention disease outbreaks.

Language: Английский

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Unlocking the puzzle: non-defining mutations in SARS-CoV-2 proteome may affect vaccine effectiveness

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: Aug. 15, 2024

Introduction SARS-CoV-2 variants are defined by specific genome-wide mutations compared to the Wuhan genome. However, non-clade-defining may also impact protein structure and function, potentially leading reduced vaccine effectiveness. Our objective is identify across entire viral genome rather than focus on individual that be associated with failure examine physicochemical properties of resulting amino acid changes. Materials methods Whole-genome consensus sequences from COVID-19 patients were retrieved GISAID database. Analysis focused Dataset_1 (7,154 genomes Italy) Dataset_2 (8,819 Spain). Bioinformatic tools identified changes codon frequencies 10% or higher, organized into sets based identical combinations. Results Non-defining in belonging clades 21 L (Omicron), 22B/22E 22F/23A (Omicron) 21J (Delta) failure. Four significantly linked low coverage: one clade 21L L3201F (ORF1a), A27- (S) G30- (N); two shared 22B 22E (S), I68- R346T set 22F 23A containing F486P (N). Booster doses showed a slight improvement protection against Omicron clades. Regarding exhibited combination non-clade P2046L P2287S L829I (ORF1b), T95I Y145H R158- Q9L (N), was Discussion Vaccine coverage associations appear influenced harbored marketed vaccines. An analysis revealed primarily hydrophobic polar substitutions occurred. results suggest non-defining proteome could affect extent vaccine. In addition, alteration characteristics acids disrupt function both.

Language: Английский

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SARS-CoV-2 variants and genomic surveillance in the low-resource north-west region of Pakistan

Biotechnology & Biotechnological Equipment, Journal Year: 2024, Volume and Issue: 38(1)

Published: Sept. 10, 2024

Language: Английский

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Analysis the molecular similarity of least common amino acid sites in ACE2 receptor to predict the potential susceptible species for SARS-CoV-2

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

Published: Oct. 16, 2023

Abstract This research offers a bioinformatics approach to forecasting both domestic and wild animals’ likelihood of being susceptible SARS-CoV-2 infection. Genomic sequencing can resolve phylogenetic relationships between the virus host. The genome sequence is highly interactive with specific region ACE2 receptor host species. We further evaluate this concept identify most important binding amino acid sites in through common similarity last (LCAS) known Therefore, viral genomic interacting key human was summarized compared other reported identified 10 significant for interaction infection from based on LCAS pattern sensitive hosts. were sequences unknown species (LCAP). predicted probability risk pattern. method be used as screening tool assess animals prevent outbreaks Graphical abstract

Language: Английский

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In silico identification of deep-sea fungal alkaloids as potential inhibitors of SARS-CoV-2, Delta and Omicron spikes

Future Virology, Journal Year: 2023, Volume and Issue: 18(14), P. 933 - 946

Published: Oct. 1, 2023

Aim: Virtual screening of deep-sea fungal metabolites against SARS-CoV-2 Delta and Omicron spikes as potential antivirals. Materials & methods: Deep-sea alkaloids (n ≥ 150) were evaluated SARS-CoV-2, spikes, using various in silico approaches, including Admet scores, physiochemical properties, molecular docking (MD) MD simulation (150 ns). Results: The test complied with scores properties within acceptable ranges, followed Lipinski's rule five. Of these, Cladosporium sphaerospermum-derived cladosin K (tetramate alkaloid) for Cystobasidium laryngis-derived saphenol (phenazine Chaetomium globosum-derived chaetoglobosin E (quinoline identified spike-inhibitors. Conclusion: Our data therefore, strongly warrants further experimental validations K, E, especially the spikes.

Language: Английский

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