An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants

Pathogens, Journal Year: 2025, Volume and Issue: 14(1), P. 23 - 23

Published: Jan. 1, 2025

The COVID-19 pandemic has posed a significant threat to global health systems, with extensive impacts across many sectors of society. been responsible for millions deaths worldwide since its first identification in late 2019. Several actions have taken prevent the disease, including unprecedented fast development and vaccination campaigns, which were pivotal reducing symptoms deaths. Given impact pandemic, continuous changes virus, present vaccine technologies, this review analyzes how, so far, we met challenge by emergence new variants discusses how next-generation pan-coronavirus vaccines, enhanced longevity breadth immune responses, may be tackled alternative administration routes antigen delivery platforms. By addressing these critical aspects, aims contribute ongoing efforts achieve long-term control COVID-19, stimulating discussion work on vaccines capable facing future waves infection.

Language: Английский

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Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 6, 2024

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage uniquely large genomic database SARS-CoV-2, we examine impact mutations across spectrum viable amino acid sequences on biophysical phenotypes highly expressed multifunctional nucleocapsid protein. We find variation in physicochemical parameters its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur related coronaviruses. In experiments with several N-protein species carrying associated major variants, point IDRs can have nonlocal modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, liquid-liquid phase separation. Omicron variant, distant different compensatory effects shifting delicate balance interactions controlling assembly properties, include creation new protein-protein interaction interface N-terminal IDR through defining P13L mutation. A picture emerges where genetic accompanied by significant characteristics species, particular IDRs.

Language: Английский

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Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2935 - 2935

Published: March 2, 2024

Blocking the interaction between SARS-CoV-2 spike protein and human angiotensin-converting enzyme II (hACE2) serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate symptoms of severe However, emergence variants has complicated process developing broad-spectrum drugs. As such, aim this study was to explore efficacy TCM against through targeting viral with hACE2 receptor. Antiviral activity systematically evaluated using pseudovirus system. Scutellaria baicalensis (S. baicalensis) found be effective infection, it mediated protein. Moreover, active molecules S. were identified analyzed. Baicalein baicalin, flavone glycoside in baicalensis, respectively, exhibited strong inhibitory activities protein, respectively. Under optimized conditions, virus infection inhibited by 98% via baicalein-treated baicalin-treated hACE2. In summary, we potential inhibitors from that mediate Omicron Future studies on application baicalein baicalin are needed.

Language: Английский

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Role of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic

Journal of Infection, Journal Year: 2024, Volume and Issue: 88(5), P. 106150 - 106150

Published: April 1, 2024

ObjectivesThe SARS-CoV-2 pandemic and large-scale genomic surveillance provided an exceptional opportunity to analyze mutations that appeared over three years in viral genomes. Here we studied their epidemic consequences for genomes from our center.MethodsWe analyzed 61,397 sequenced respiratory samples surveillance. Mutations frequencies were calculated using Nextclade, Microsoft Excel, in-house Python script.ResultsA total of 22,225 nucleotide identified, 220 (1.0%) being each at the root ≥836 genomes, classifying as 'hyperfertile'. Two seeded European pandemic: P323L RNA polymerase, associated with increased mutation rate, D614G spike improved fitness. Most 'hyperfertile' occurred areas not predicted virulence. Their mean number was 8±6 (0-22) per 1,000 nucleotides gene. They 3.7-times more frequent accessory than informational genes (13.9 versus 3.7/1,000 nucleotides). Particularly, they 4.1-times ORF8 polymerase Interestingly, stop codons present 97 positions, almost only genes, including (21/100 codons).Conclusionsmost did predict emergence a new epidemic, some indicating existence so-named 'non-virulence' genes.

Language: Английский

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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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Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2

eLife, Journal Year: 2024, Volume and Issue: 13

Published: June 28, 2024

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage uniquely large genomic database SARS-CoV-2, we examine impact mutations across spectrum viable amino acid sequences on biophysical phenotypes highly expressed multifunctional nucleocapsid protein. We find variation in physicochemical parameters its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur related coronaviruses. In experiments with several N-protein species carrying associated major variants, point IDRs can have nonlocal modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, liquid-liquid phase separation. Omicron variant, distant different compensatory effects shifting delicate balance interactions controlling assembly properties, include creation new protein-protein interaction interface N-terminal IDR through defining P13L mutation. A picture emerges where genetic accompanied by significant characteristics species, particular IDRs.

Language: Английский

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Structural and Conformational Impact of Deleterious Spike Protein Mutations in SARS-CoV-2 Omicron Lineages

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

A large number of mutations in the Spike (S) protein SARS-CoV-2 omicron variant have been noted to alter receptor binding domain (RBD) and increase surface enhance opening pocket. The cumulative effect S1 S2 subunit can influence conformational dynamics surface, facilitating release viral genome into host cells. This study investigates deleterious across all Omicron lineages identified our analysis their on stability RBD opening. Whole Genome Sequencing 231 positive patients Karachi, Pakistan, were performed using Illumina Miseq instrument raw reads analyzed viralrecon pipeline. mutational effects S protein, including wild-type (7FG7), close (6VXX) open (6VYB) states, assessed through MD simulations. Four missense (Tyr505His, Asn764Lys, Asp950Asn, Asn969Lys) variant. In wildtype state mutant models, Tyr505His, Asp950Asn Asn969Lys caused destabilizing effects, higher RMSDs vs. wild-type, fluctuations (438-510) region (946-1010), compared native structure. These increased pocket propensity model conformation (6VYB). structural change promoted trimer α-helix movement away from region. closed state, only (Asp950Asn lead predicted destabilization protomer C towards B (RBD region). are stabilize "down" potentially enhancing spike antigenic heterogeneity. highlighted (Tyr505His) subunits different controlling its presentation receptors. Future experimental studies needed elucidate biological significance these alterations, particularly by establishing a link between impact biology.

Language: Английский

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SARS-CoV-2 Genetic Variants Identified in Selected Regions of Ethiopia Through Whole Genome Sequencing: Insights from the Fifth Wave of COVID-19

Genes, Journal Year: 2025, Volume and Issue: 16(3), P. 351 - 351

Published: March 18, 2025

Background: The COVID-19 pandemic highlighted SARS-CoV-2 variants with increased transmissibility and immune evasion. In Ethiopia, where cases surged, the understanding of virus’s dynamics was limited. This study analyzed during fifth wave, crucial for guiding vaccines, therapeutics, diagnostics, disease severity. Method: From June to August 2022, 150 SARS-CoV-2-positive samples were randomly selected from Ethiopian Public Health Institute repository. Sixty-three high-quality genome sequences analyzed. Results: Of 63 sequences, 70% males 30% females, a median age 34. Omicron dominated (97%, 61/63), primarily clade 22A (64%, 40/63), followed by 22B (18%, 11/63) 21K (14%, 9/63). Delta accounted 3.2% (2/63). identified in all (25) vaccinated participants. showed limited evolutionary divergence lower genetic diversity compared global sequences. Conclusion: predominant variant Ethiopia’s indicating recent community transmission. Despite minor differences, ongoing surveillance remains critical tracking informing public health interventions.

Language: Английский

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Diversity of short linear interaction motifs in SARS-CoV-2 nucleocapsid protein

mBio, Journal Year: 2023, Volume and Issue: 14(6)

Published: Nov. 29, 2023

ABSTRACT Molecular mimicry of short linear interaction motifs has emerged as a key mechanism for viral proteins binding host domains and hijacking cell processes. Here, we examine the role RNA virus sequence diversity in dynamics virus-host interface by analyzing uniquely vast record viable SARS-CoV-2 species with focus on multi-functional nucleocapsid protein. We observe abundant presentation encoding several essential protein interactions, alongside majority possibly non-functional randomly occurring motif sequences absent subsets species. A large number emerge ex nihilo through transient mutations relative to ancestral consensus sequence. The observed mutational landscape implies an accessible space that spans at least 25% known eukaryotic motifs. This reveals highly dynamic process capacity broadly explore motifs, allowing rapidly evolve interface. IMPORTANCE Short (SLiMs) are 3–10 amino acid long intrinsically disordered regions (IDRs) serve ubiquitous protein-protein modules cells. Through molecular mimicry, viruses hijack these control cellular It is thought small size SLiMs high mutation frequencies IDRs allow rapid adaptation. However, salient characteristic viruses, due replication errors, their obligate existence mutant swarms. Taking advantage genomic database SARS-CoV-2, here, analyze SLiMs, focusing abundant, find produces abundance transiently present allows efficiently host-virus

Language: Английский

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Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3696 - 3696

Published: March 26, 2024

SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and appear be critical coronavirus’s macro- microevolution. Understanding molecular mechanisms of mutational hotspots (positions, loci with recurrent mutations, nucleotide context) is important disentangling roles mutagenesis In genome, deletions insertions are frequently associated repetitive sequences, whereas C>U often surrounded by nucleotides resembling APOBEC mutable motifs. We describe various approaches mutation spectra analyses, including context features RNAs that likely involved generation mutations. also discuss interplay between selection as a complex evolutionary trend. The substantial variability complexity pipelines reconstruction huge number genomic sequences major problems analyses genome. As solution, we advocate development centralized database predicted which needs updated on regular basis.

Language: Английский

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