SARS-CoV-2 CoCoPUTs: Analyzing GISAID and NCBI data to obtain codon statistics, mutations, and free energy over a multi-year period

Virus Evolution, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

A consistent area of interest since the beginning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been sequence composition virus and how it changed over time. Many resources have developed for storage analysis SARS-CoV-2 data, such as GISAID (Global Initiative on Sharing All Influenza Data), NCBI, Nextstrain, outbreak.info. However, relatively little done to compile codon usage codon-level mutation secondary structure data into a single database. Here, we assemble aforementioned many additional attributes in new database entitled CoCoPUTs. We begin with an overview overlap between two largest sources data: NCBI Virus (GenBank). then evaluate different types curation strategies reduce dataset millions sequences only one per Pango lineage variant. performed specific analyses coding (CDSs), including calculating usage, pair dinucleotides, junction mutations, GC content, effective number codons (ENCs), pairs (ENCPs). also whole-genome RNA prediction calculations each variant, using LinearPartition software modified selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) that are available online. Finally, compiled all our resource, CoCoPUTs, paired resulting statistics variant proportion time order derive trends viral evolution. Although overall did not change drastically, line previous literature this subject, observe while GC% content decreased, third position was more positive relative February 2021 July 2023. Over same interval, noted both synonymous nonsynonymous mutations increased number, outpacing at rate 3:1. predicted structures nearly contained previously described virus-activated inhibitor translation (VAIT) stem loops, validating first their existence variants (as opposed local predictions). separately produced mutation-deprived set repeated set. This revealed interesting trend reduced ensemble free energy compared unaltered structures, indicating play role increasing molecules. These validate studies describing increases human viruses indicate possible biology.

Language: Английский

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A brief guide for gene delivery to the brain using adeno-associated viral vectors

Molecules and Cells, Journal Year: 2025, Volume and Issue: unknown, P. 100189 - 100189

Published: Feb. 1, 2025

Language: Английский

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Gene mutation estimations via mutual information and Ewens sampling based CNN & machine learning algorithms

Journal of Applied Statistics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 33

Published: Feb. 3, 2025

Language: Английский

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Codon usage bias and nucleotide bias are not influenced by the 5′ flanking but by 3′ and intronic region composition in SCID-associated genes

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142182 - 142182

Published: March 1, 2025

Language: Английский

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Subtractive proteomics and reverse-vaccinology approaches for novel drug targets and designing a chimeric vaccine against Ruminococcus gnavus strain RJX1120

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 14, 2025

Mediterraneibacter gnavus , also known as Ruminococcus is a Gram-positive anaerobic bacterium that resides in the human gut microbiota. Notably, this plays dual roles health and disease. On one side it supports nutrient metabolism essential for bodily functions on other contributes to development of Inflammatory Bowel Disease (IBD) gastrointestinal disorders. R. strain RJX1120 an encapsulated has been linked develop IBD. Despite advances made its role homeostasis, limited information available strain-specific virulence factors, metabolic pathways, regulatory mechanisms. The study such aspects crucial make microbiota-targeted therapy understand implications host health. A multi-epitope vaccine against was designed using reverse vaccinology-based subtractive proteomics approach. Among 3,219 proteins identified RJX1120, two critical virulent antigenic proteins, Single-stranded DNA-binding protein SSB (A0A2N5PT08) Cell division ATP-binding FtsE (A0A2N5NK05) were screened potential targets. predicted B-cell T-cell epitopes from these immunological properties antigenicity, allergenicity, solubility, MHC binding affinity, toxicity. Epitopes chosen cross-linked suitable spacers adjuvant vaccine. Structural refinement construct revealed 95.7% amino acid residues located favored regions, indicating high-quality structural model. Molecular docking analysis demonstrated robust interaction between Toll-like receptor 4 (TLR4), with energy −1277.0 kcal/mol. results molecular dynamics simulations further confirmed stability vaccine-receptor complex under physiological conditions. In silico cloning yielded GC content 48% Codon Adaptation Index (CAI) value 1.0, optimal expression system. These indicate possibility candidate prevention -associated diseases. However, experimental validation required confirm immunogenicity protective efficacy.

Language: Английский

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Comparison of the L3-23K and L5-Fiber Regions for Arming the Oncolytic Adenovirus Ad5-Delta-24-RGD with Reporter and Therapeutic Transgenes

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3700 - 3700

Published: April 14, 2025

The insertion of a transgene downstream the L3-23K or L5-Fiber region was reported as vital strategy for arming E3 non-deleted oncolytic adenoviruses. However, depending on percentage codons with G/C at third base position (GC3%) and type splicing acceptor, an insert may substantially affect virus fitness. Since transgenes regions has never been compared in terms their expression levels impact fitness, we assessed total yield, cytolytic efficacy, plaque size Ad5-delta-24-RGD (Ad5Δ24RGD) armed EGFP, FLuc, suppressor RNA silencing p19, soluble wild-type human/mouse high-affinity human programmed cell death receptor-1 (PD-1/PDCD1) ectodomains, hyaluronidase PH20/SPAM1. ensures production considerably higher levels. either differentially unpredictably affects potency Ad5Δ24RGD, which cannot be explained by GC3% level alone. Surprisingly, mouse PD-1 ectodomains 83.1% 70.1% GC3%, respectively, does not efficacy but increases line-dependent manner.

Language: Английский

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Unlocking the power of antimicrobial peptides: advances in production, optimization, and therapeutics

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: April 28, 2025

Antimicrobial peptides (AMPs) are critical effectors of innate immunity, presenting a compelling alternative to conventional antibiotics amidst escalating antimicrobial resistance. Their broad-spectrum efficacy and inherent low resistance development countered by production challenges, including limited yields proteolytic degradation, which restrict their clinical translation. While chemical synthesis offers precise structural control, it is often prohibitively expensive complex for large-scale production. Heterologous expression systems provide scalable, cost-effective platform, but necessitate optimization. This review comprehensively examines established emerging AMP strategies, encompassing fusion protein technologies, molecular engineering approaches, rational peptide design, post-translational modifications, with an emphasis on maximizing yield, bioactivity, stability, safety. Furthermore, we underscore the transformative role artificial intelligence, particularly machine learning algorithms, in accelerating discovery optimization, thereby propelling expanded therapeutic application contributing global fight against drug-resistant infections.

Language: Английский

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Viral Infections and Their Ability to Modulate Endoplasmic Reticulum Stress Response Pathways

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1555 - 1555

Published: Sept. 30, 2024

In eukaryotic cells, the endoplasmic reticulum is particularly important in post-translational modification of proteins before they are released extracellularly or sent to another endomembrane system. The correct three-dimensional folding most occurs ER lumen, which has an oxidative environment that essential for formation disulfide bridges, maintaining protein structure. a versatile organelle ensures structure and synthesis lipids sterols, addition offering support maintenance intracellular calcium. Consequently, cells needed respond demands caused by physiological conditions pathological disturbances homeostasis, leading proper functioning cell even programmed death. Disturbances function trigger response accumulation unfolded misfolded proteins, known as response. Such include abiotic stress, pharmacological agents, pathogens, such viruses. When accumulate ER, can undergo ubiquitination proteasomal degradation through components ER-associated Once prolonged activity UPR pathway occurs, indicating homeostasis cannot be reestablished, this induce death apoptosis. Here, we discuss how viruses have evolved ways counteract responses maximize replication. This evolutionary viral ability understand pathology should taken into account when designing therapeutic interventions vaccines.

Language: Английский

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The complete chloroplast genome sequences of 11 Panax species: Providing insights for evolution and species identification

Industrial Crops and Products, Journal Year: 2024, Volume and Issue: 223, P. 120160 - 120160

Published: Dec. 10, 2024

Language: Английский

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Codon-Optimized and de novo-Synthesized E-Selectin/AAV2 Dose-Response Study for Vascular Regeneration Gene Therapy

Annals of Surgery, Journal Year: 2024, Volume and Issue: 280(4), P. 570 - 583

Published: July 8, 2024

Objective: This study focuses on dose–response investigation using a codon-optimized and de novo–synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug enabling of subsequent clinical studies. Background: Gene therapy is potential solution patients suffering from chronic limb-threatening ischemia. Understanding the dose effective gene delivery crucial future Drug–enabling Methods: Expression E-Selectin was assessed by flow cytometry following vitro cell transfection assay RT-qPCR murine limbs injected vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose–response studies involved 3 cohorts FVB/NJ mice (n=6/group) escalating log doses intramuscularly divided aliquots, ranging 2 × 10 9 VG to 11 VG, into ischemic created left femoral artery/vein ligation/excision administration nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent gangrene free limb, functional limb recovery, therapeutic angiogenesis were assessed. Results: Codon-optimized E-Sel/AAV2 exhibits superior expression level than WT both vivo. Mice treated high (2 VG) showed significantly improved perfusion indices, lower Faber scores, increased running stamina, neovascularization compared tested control groups, indicating distinct dose-dependent response. No toxicity detected any animal groups studied. Conclusions: Vascular Regeneration Therapy holds promise enhancing recovery hindlimb function, identified this as aliquots intramuscularly.

Language: Английский

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