Ask about this productRelated genes to: ISG15 Blocking Peptide
- Gene:
- ISG15 NIH gene
- Name:
- ISG15 ubiquitin like modifier
- Previous symbol:
- G1P2
- Synonyms:
- IFI15, UCRP
- Chromosome:
- 1p36.33
- Locus Type:
- gene with protein product
- Date approved:
- 1990-10-16
- Date modifiied:
- 2019-04-23
Related products to: ISG15 Blocking Peptide
Related articles to: ISG15 Blocking Peptide
- The SARS-CoV-2 papain-like protease (PL) and the main protease (M) catalyze hydrolysis of the viral polyproteins pp1a/1ab into functional nonstructural proteins. PL and M are medicinal chemistry targets, with M inhibitors being used for COVID-19 treatment. PL also catalyzes hydrolysis of ubiquitin and interferon-stimulated gene 15 (ISG15) from post-translationally modified human proteins. Here we report how screening of reported deubiquitinase inhibitors using solid-phase extraction coupled to mass spectrometry assays with oligopeptide substrates based on pp1a/1ab and on an ISG15-modified human protein enabled the identification of substrate-selective PL inhibitors. The results reveal that the deubiquitinase inhibitor ML364 selectively inhibits the deISGylase activity of isolated PL over its pp1a/1ab-processing activity. Structure-activity relationship and computational studies support the assignment of ML364 and derivatives as substrate-selective PL inhibitors. The combined results provide proof-of-concept for developing substrate-selective inhibitors of PL and, by implication, related proteolytic enzymes, including deubiquitinases. - Source: PubMed
Publication date: 2026/06/12
Sharma SakshiWing Peter A CTrede WojtekBasak ShyamDraganov Simeon DAndrews-Clark TaylahSalah EidarusLukacik PetraStrain-Damerell ClairePinto-Fernández AdánWalsh Martin ADuarte FernandaSchofield Christopher JBrewitz Lennart - Nervous necrosis virus (NNV), a member of the family Nodaviridae, is a devastating pathogen in global aquaculture, yet effective preventive and therapeutic strategies remain limited. This study aimed to identify natural compounds that inhibit NNV infection by targeting the host receptor Lateolabrax japonicus heat shock protein 90 alpha family class B1 (LjHSP90ab1). Herein, we identified curcumin and silybin as potent inhibitors of LjHSP90ab1. Molecular docking predicted that curcumin and silybin bind to the N-terminal and C-terminal domains of LjHSP90ab1, respectively, and fluorescence spectroscopy confirmed their direct binding to the protein. These interactions disrupted the binding of NNV capsid protein (CP) to LjHSP90ab1, blocking viral entry. In vitro assays showed that both compounds significantly suppressed NNV proliferation, and their combination exhibited synergistic efficacy. Furthermore, both compounds upregulated the expression of critical antiviral genes, including interferon (IFN), interferon-stimulated gene 15 (ISG15), virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin), and myxovirus resistance (Mx). In vivo, bath treatment with curcumin, silybin, or their combination significantly improved survival rates of NNV-infected L. japonicus from 25.93% (infected control) to 48.15%, 40.74%, and 51.85%, respectively, and reduced viral load and tissue damage. Collectively, our findings demonstrated that curcumin and silybin exert dual antiviral effects by blocking viral entry via LjHSP90ab1 targeting and enhancing host immunity, highlighting their potential as environmentally friendly agents for NNV control in aquaculture. - Source: PubMed
Publication date: 2026/06/11
Yang XiaogangGao HuanYi MeishengJia Kuntong - Two hundred Holstein dairy cows (milk yield of 34.5 ± 0.6 kg/d, 3.1 ± 1.2 lactations) were enrolled to investigate the role of WNTs signaling network in early pregnancy loss. The ISG15 mRNA abundance of uterine luminal cells obtained via brushing on day 16 after service was used to determine initial pregnancy status, with confirmation via ultrasound on days 32 and 60. The mRNA abundance of cells obtained from uterine brushing for WNT2, WNT5A, WNT7A, WNT11, frizzled receptors (FZD), dickkopf proteins (DKK1), Kremen and LDL receptor related protein (LRP 5/6), lymphoid enhancer-binding factor 1 (LEF1) and transcription factor 7 (TCF) was determined at day16 after insemination. Relative mRNA abundance of DKK1 (1.98-fold), WNT5A (2.67-fold), WNT7A (1.83-fold) and WNT11 (2.16-fold) genes in pregnant cows were significantly greater than in cows with early embryonic mortality (P < 0.05). In contrast, relative mRNA abundance of WNT2 (3.35-fold) and FZD6 (5.50-fold) genes were significantly greater in pregnant-embryo loss cows compared to pregnant cows on day 16 (P < 0.05). The relative mRNA abundance of LRP5, LRP6, LEF1, FZD3, FZD5, FZD8 and TCF genes were not affected by pregnancy status although their variances were lower; however, there was a negative correlation among ISG15 and these genes. In conclusion, differences in mRNA abundance of WNT signaling genes in uterine brushing samples are associated with pregnancy status in lactating dairy cows and may contribute to minimizing early bovine pregnancy losses. - Source: PubMed
Publication date: 2026/06/04
Dirandeh EAnsari-Pirsaraei ZThatcher W W - The tumorigenesis and progression of conventional cervical squamous cell carcinoma generally follow a well-defined cascade: from normal cervix uteri to high-grade cervical intraepithelial neoplasia (precancer), cervical carcinoma in situ, and ultimately invasive cervical carcinoma. However, biomarkers and targets that reflect tumor evolution during CSCC progression at different time points within the same patient remain lacking. We integrated single-cell RNA sequencing with spatial transcriptomics from a series of human cervix uteri tissues spanning the cascade of cervical premalignant lesions and malignant progression obtained from the same patients. We found that fibroblasts and endothelial cells decreased, whereas immune cells (mainly T cells and B cells) increased during CSCC development. Moreover, the immune response-related GNLY-fibroblasts and GNLY-endothelial cells were significantly enriched during the PCT of CSCC. Additionally, a panel of gene signatures (CLDN1, ISG15, PTGDS) with clinical significance for the precise diagnosis and personalized treatment strategies of PCT was identified. This gene panel may serve as an auxiliary diagnostic indicator in cervical biopsy specimens and help identify lesions associated with malignant progression. CLDN1 and ISG15 promote CSCC progression, whereas PTGDS suppresses it. Moreover, ISG15, synthesized by inflammatory cancer-associated fibroblasts (CAFs), enhances the stability of FGF1, thereby activating the FGF1/FGFR1/PI3K/AKT/mTOR signaling pathway. FGFR1 and PI3K/AKT/mTOR inhibitors were found to suppress CSCC cell proliferation in vitro and tumor growth in vivo. High ISG15 and CLDN1 expression correlated with poor survival in cervical cancer tissue microarrays and with reduced immunotherapy response in exploratory public datasets, pending validation in CSCC cohorts. Our study defines the ecosystem of PCT from cell subpopulations, the communicating gene networks, and key signal transductions involved in PCT of CSCC. These findings offer new insights into the spatiotemporal evolution of the human cervix in premalignant and malignant lesions, paving the way for improved CSCC diagnosis and therapy. - Source: PubMed
Publication date: 2026/06/09
Zhou YubingLuo YanlinGe YunxiaoWu XinxinWu RuiLiu HangruiTang LinLi YuanyingRen ChenchenZeng XianxuHu YameiLiu KangdongLiu HuiDong Zigang - Dengue virus (DENV) is responsible for hundreds of millions of infections per year, but no clinically approved antiviral therapy exists, and direct-acting candidates are limited by toxicity and viral genetic diversity. Traditional medicinal preparations such as Nimba/Neem (Azadirachta indica) and polyherbal Ayurvedic preparation Triphala (a combination of Terminalia chebula, Terminalia bellirica and Phyllanthus emblica) contain multiple metabolites with antiviral and antioxidant properties but their mechanisms of action are not fully characterised. Here, we combined cell-based antiviral assays with transcriptome profiling to compare how Nimba and Triphala shape host responses during DENV infection in RAW264.7 macrophages, a key innate immune target. Nimba and Triphala demonstrated low cytotoxicity in the concentrations of our assays, which supports a favourable therapeutic window. The RNA-seq analysis showed that Nimba induced broader transcriptional reprogramming in DENV-infected macrophages than Triphala, with 4,182 differentially expressed genes in the NB + DV versus DV comparison, indicating a stronger host transcriptional impact during infection. It increased interferon-stimulated gene (Isg15) programs and attenuated inflammatory signalling (e.g., Cxcl10), oxidative stress (Txnip, Aox4, Phlda3), and endoplasmic reticulum stress pathways (Trib3) upon infection. Triphala, in contrast, caused relatively restrained baseline transcriptional reprogramming and a more selective infection-context response. Docking analysis suggested that Triphala-associated metabolites may engage multiple DENV proteins. In line with this, molecular docking of nine proteins of DENV indicated multi-target binding of Triphala metabolites, with corilagin showing favorable predicted binding affinities (ΔG -13.9 kcal/mol), in certain proteins, superior to that of reference compounds (Remdesivir and NITD008). Together, these data support broader host-response modulation by Nimba and a more selective host response with a possible virus-directed contribution for Triphala during DENV infection and lay the foundational research for synthesis of anti-viral herbal formulations using Nimba and Triphala ingredients. - Source: PubMed
Publication date: 2026/06/05
Chakraborty DebayaniNamitha RRoy RahulDevi K Lavanya