Phenotypic Test of Benzo[4,5]imidazo[1,2-c]pyrimidinone-Based Nucleoside and Non-Nucleoside Derivatives against DNA and RNA Viruses, Including Coronaviruses DOI Open Access

Polina N. Kamzeeva,

Ivan Petushkov,

Ekaterina Knizhnik

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14540 - 14540

Published: Sept. 26, 2023

Emerging and re-emerging viruses periodically cause outbreaks epidemics around the world, which ultimately lead to global events such as COVID-19 pandemic. Thus, urgent need for new antiviral drugs is obvious. Over more than a century of development, nucleoside analogs have proven be promising agents against diversified DNA RNA viruses. Here, we present synthesis evaluation activity their deglycosylated derivatives based on hydroxybenzo[4,5]imidazo[1,2-c]pyrimidin-1(2H)-one scaffold. The was evaluated panel structurally phylogenetically diverse leader compound showed micromolar representatives family Coronaviridae, including SARS-CoV-2, well respiratory syncytial virus in submicromolar range without noticeable toxicity host cells. Surprisingly, methylation aromatic hydroxyl group resulted varicella-zoster any significant impact cell viability. shown weak inhibitor SARS-CoV-2 RNA-dependent polymerase. It also inhibited biocondensate formation important replication. active compounds may considered good starting point further structure optimization mechanistic preclinical studies.

Language: Английский

Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets DOI Creative Commons
Soyoung Jeon, Yong‐Duck Chung, Jae‐Sung Lim

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 6, 2025

Cells orchestrate their processes through complex interactions, precisely organizing biomolecules in space and time. Recent discoveries have highlighted the crucial role of biomolecular condensates-membrane-less assemblies formed condensation proteins, nucleic acids, other molecules-in driving efficient dynamic cellular processes. These condensates are integral to various physiological functions, such as gene expression intracellular signal transduction, enabling rapid finely tuned responses. Their ability regulate signaling pathways is particularly significant, it requires a careful balance between flexibility precision. Disruption this can lead pathological conditions, including neurodegenerative diseases, cancer, viral infections. Consequently, emerged promising therapeutic targets, with potential offer novel approaches disease treatment. In review, we present recent insights into regulatory mechanisms by which influence pathways, roles health disease, strategies for modulating condensate dynamics approach. Understanding these emerging principles may provide valuable directions developing effective treatments targeting aberrant behavior diseases.

Language: Английский

Citations

1
A NOVEL AND QUICK EGG YOLK IMMUNOGLOBULIN Y ANTIBODY EXTRACTION METHOD LEVERAGING THE PROTEIN LIQUID-LIQUID PHASE SEPARATION PRINCIPLE DOI Creative Commons
Murtala Bindawa Isah,

Hu Yuzhang,

Mei Dang

et al.

Poultry Science, Journal Year: 2025, Volume and Issue: 104(2), P. 104804 - 104804

Published: Jan. 11, 2025

This study presents a novel and efficient method for extracting immunoglobulin Y (IgY) antibodies from egg yolk based on the principle of liquid-liquid phase separation (LLPS) induced by polyethylene glycol 8000 (PEG 8000). Initial delipidation samples with varying PEG concentrations demonstrated optimal efficiency protein recovery at 2.5 % concentration. Subsequent IgY extraction involved inducing LLPS raising concentration to 6.5 %, resulting in turbid solutions formation globular droplet-like condensates observed under microscope. Unlike 6000 that aggregation, developed here using does not lead appearance aggregates IgY. SDS-PAGE analysis confirmed extracted was no different conventional method, similar purity levels (77 vs 79 %). Enzyme-linked immunosorbent assay western blot antigen recognition properties isolated significantly reduces amount used, leading substantial cost savings compared 6000. The can be completed within one hour. Despite slightly lower yield time- cost-saving advantages this make it promising alternative research. proposed technique utilizing has potential improve physicochemical optimized production, while offering quicker cost-effective solution various applications biomedical

Language: Английский

Citations

1
Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation DOI

Ahmed Eltayeb,

Faisal Al‐Sarraj, Mona G. Alharbi

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 13, 2024

Abstract When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has wide spectrum of clinical manifestations, from no symptoms acute respiratory distress syndrome. The initiates damage by attaching ACE‐2 protein on surface endothelial cells line blood vessels and using these as hosts for replication. Reactive oxygen species levels are increased during viral replication, which oxidative stress. About three‐fifths (~60%) people who get infected with eradicate their body after 28 days recover normal activity. However, large fraction (~40%) suffer various (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, tachycardia) beyond 12 weeks diagnosed syndrome long COVID. Long‐term studies in group contracted have been contrasted noninfected matched people. A subset can be distinguished set cytokine markers persistent, low‐grade inflammation often self‐report two or more bothersome symptoms. No medication alleviate efficiently. Coronavirus nucleocapsid proteins investigated extensively potential drug targets due key roles among is ability bind respective genomic RNAs incorporation into emerging virions. This review highlights basic its undergo liquid–liquid phase separation. We hypothesize this separation may contribute hypothesis unlocks new investigation angles could potentially open novel avenues better understanding COVID treating condition.

Language: Английский

Citations

6
Anti-virus Activity and Mechanisms of Natural Polysaccharides from Medicinal Herbs DOI
Xiaoyan Huang,

Xingyin Chen,

Yuanhua Xian

et al.

Carbohydrate Research, Journal Year: 2024, Volume and Issue: 542, P. 109205 - 109205

Published: July 6, 2024

Language: Английский

Citations

4
The prognostic value of the platelet-to-lymphocyte ratio in multiple myeloma patients treated with a bortezomib-based regimen DOI Creative Commons
Q. Zhang, Yifan Wang, Wenting Shi

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 13, 2025

Multiple myeloma (MM) is the second most common hematological malignancy. Previous studies have validated prognostic significance of platelet-to-lymphocyte ratio (PLR) in patients with certain solid tumors. However, relationship between PLR and prognosis has not been clearly demonstrated. In our study, we included 122 newly diagnosed MM who were treated bortezomib-based chemotherapy. These divided into low-PLR high-PLR groups based on their initial values. We compared clinical characteristics two utilized restricted cubic splines (RCSs) regression model to estimate nonlinear overall survival (OS) patients. The results showed that group had significantly worse OS (P = 0.00031) progression-free (PFS) < 0.0001) those group. Furthermore, within higher-risk group, a low was also associated 0.0037) PFS 0.0048). Therefore, identified as an independent predictor poor RCS curves further confirmed significant MM. may serve indicator for undergoing chemotherapy, there exists crucial these

Language: Английский

Citations

0
Peptide-Mediated Liquid-Liquid Phase Separation and Biomolecular Condensates DOI

Guangle Li,

Chengqian Yuan, Xuehai Yan

et al.

Soft Matter, Journal Year: 2025, Volume and Issue: 21(10), P. 1781 - 1812

Published: Jan. 1, 2025

Peptide-mediated liquid–liquid phase separation (LLPS) underpins the formation of dynamic biomolecular condensates, regulated by diverse molecular interactions, and highlights potential applications in drug delivery synthetic biology.

Language: Английский

Citations

0
Liquid-liquid phase separation in microorganisms: insights into existence, functions, and applications DOI
Anas Yusuf,

Abdurrahman Usman,

Murtala Bindawa Isah

et al.

Microbiological Research, Journal Year: 2024, Volume and Issue: 292, P. 128026 - 128026

Published: Dec. 17, 2024

Language: Английский

Citations

1
Liquid-liquid phase separation in viral infection: from the occurrence and function to treatment potentials DOI
Zheng Cao,

Yanhua Yang,

Simeng Zhang

et al.

Colloids and Surfaces B Biointerfaces, Journal Year: 2024, Volume and Issue: 246, P. 114385 - 114385

Published: Nov. 17, 2024

Language: Английский

Citations

1
Exploring liquid-liquid phase separation-related diagnostic biomarkers in osteoarthritis based on machine learning algorithms and experiment DOI Creative Commons
Yue Li, Bo Dong

Immunobiology, Journal Year: 2024, Volume and Issue: 229(5), P. 152825 - 152825

Published: June 9, 2024

Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration and inflammation. Liquid-liquid phase separation (LLPS), biophysical process involved in cellular organization, has recently gained attention OA research. However, the relationship between LLPS remains poorly understood. We analyzed gene expression data from GSE48556 dataset to identify LLPS-related genes associated with OA. Differential analysis, enrichment analyses, machine learning algorithms were employed explore functional significance of construct diagnostic model for In addition, IL-1β as pro-inflammatory factor establish an vitro model, protein levels biomarkers detected western blot vitro. A total 145 screened samples. Enrichment analyses revealed these mainly enriched mRNA metabolic processes, cytoplasmic granules, insulin resistance. Four characteristic selected using algorithms, including ADRB2, H3F3B, GNL3L, PELO. These showed satisfactory values. Furthermore, association immune cells, T cells CD8 monocytes. experiments that stimulation significantly inhibited cell viability chondrocytes enhanced factors, could mimic inflammatory state The GNL3L H3F3B proteins group obviously lower than those control group, while ADRB2 PELO higher, which was consistent results bioinformatics analysis. Our study identifies potential findings provide insights into molecular mechanisms underlying pathogenesis offer opportunities development novel therapeutic strategies.

Language: Английский

Citations

0
Molecular Mechanisms and Potential Antiviral Strategies of Liquid–Liquid Phase Separation during Coronavirus Infection DOI Creative Commons
Ying Wang,

Liying Zhou,

Xiaohan Wu

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 748 - 748

Published: June 24, 2024

Highly pathogenic coronaviruses have caused significant outbreaks in humans and animals, posing a serious threat to public health. The rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted millions infections deaths. However, the mechanisms through which evade host’s antiviral immune system are not well understood. Liquid–liquid phase separation (LLPS) is recently discovered mechanism that can selectively isolate cellular components regulate biological processes, including host innate signal transduction pathways. This review focuses on coronavirus-induced LLPS strategies for utilizing response, along with potential therapeutic drugs methods. It aims provide more comprehensive understanding novel insights researchers studying induced by pandemic viruses.

Language: Английский

Citations

0