Exploration of Fuzheng Yugan Mixture on COVID-19 based on network pharmacology and molecular docking DOI Creative Commons
Xinyu Jiang, Jie Zhou,

Zhongming Yu

et al.

Medicine, Journal Year: 2023, Volume and Issue: 102(3), P. e32693 - e32693

Published: Jan. 20, 2023

After the World Health Organization declared coronavirus disease 2019 (COVID-19), as a global pandemic, health workers have been facing an unprecedented and severe challenge. Currently, mixturetion to inhibit exacerbation of pulmonary inflammation caused by COVID-19, Fuzheng Yugan Mixture (FZYGM), has approved for medical institution notification. However, mechanism FZYGM remains poorly defined. This study aimed elucidate molecular related physiological pathways potential therapeutic agent COVID-19. Active molecules were obtained from Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP), while target genes COVID-19 identified DrugBank GeneCards. Compound-target networks protein-protein interactions (PPI) established Cytoscape_v3.8.2 String databases, respectively. The gene ontology (GO) analysis Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment performed. Finally, more in-depth was performed using docking. Our 7 active compounds 3 corresponding core targets. main potentially acting signaling include interleukin (IL)-17 pathway, tumor necrosis factor (TNF) Toll-like receptor Th17 cell differentiation, disease-COVID-19. shows that can exhibit anti-COVID-19 effects through multiple targets pathways. Therefore, be considered drug candidate treatment it provides good theoretical support subsequent experiments clinical applications

Language: Английский

Human organoids in basic research and clinical applications DOI Creative Commons
Xiaoyan Tang,

Shanshan Wu,

Da Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 24, 2022

Abstract Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult (AdSCs) derived healthy individuals patients that recapitulate the cellular heterogeneity, structure, and functions of organs. The advent 3D organoid systems is now possible to allow remarkably detailed observation cell morphogens, maintenance differentiation resemble primary tissues, enhancing potential study both physiology developmental stage. As they similar their original organs carry genetic information, organoids patient hold great promise for biomedical research preclinical drug testing currently used personalized, regenerative medicine, gene repair transplantation therapy. In recent decades, researchers have succeeded generating various types mimicking vivo Herein, we provide an update on current technologies brain, retinal, kidney, liver, lung, gastrointestinal, cardiac, vascularized multi-lineage organoids, discuss differences between PSC- AdSC-derived summarize applications cell-derived laboratory clinic, outline challenges application which would deepen understanding mechanisms development enhance further utility basic clinical studies.

Language: Английский

Citations

240
METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection DOI Creative Commons
Na Li, Hui Hui, William A. Bray

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 35(6), P. 109091 - 109091

Published: May 1, 2021

Language: Английский

Citations

199
Organoids: The current status and biomedical applications DOI Creative Commons
Siqi Yang,

Hai‐Jie Hu,

Heng‐Chung Kung

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 17, 2023

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that derived from cells with stem potential and can self-organize differentiate into 3D cell masses, recapitulating the morphology functions their in vivo counterparts. Organoid culture is an emerging technology, organoids various tissues, such as brain, lung, heart, liver, kidney, have been generated. Compared traditional bidimensional culture, organoid systems unique advantage conserving parental gene expression mutation characteristics, well long-term maintenance function biological characteristics vitro. All these features open up new opportunities for drug discovery, large-scale screening, precision medicine. Another major application disease modeling, especially hereditary diseases difficult to model vitro modeled by combining genome editing technologies. Herein, we introduce development current advances technology field. We focus on applications basic biology clinical research, also highlight limitations future perspectives. hope this review provide a valuable reference developments organoids.

Language: Английский

Citations

104
Human organoid models to study SARS-CoV-2 infection DOI Open Access
Yuling Han, Liuliu Yang, Lauretta A. Lacko

et al.

Nature Methods, Journal Year: 2022, Volume and Issue: 19(4), P. 418 - 428

Published: April 1, 2022

Language: Английский

Citations

99
iPSC‐derived human cortical organoids display profound alterations of cellular homeostasis following SARS‐CoV‐2 infection and Spike protein exposure DOI Creative Commons
Gioia Cappelletti,

Lorenzo Brambilla,

Sergio Strizzi

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(4)

Published: Feb. 14, 2025

Abstract COVID‐19 commonly leads to respiratory issues, yet numerous patients also exhibit a diverse range of neurological conditions, suggesting detrimental impact SARS‐CoV‐2 or the viral Spike protein on central nervous system. Nonetheless, molecular pathway behind pathology and presumed neurotropism remains largely unexplored. We generated human cortical organoids (HCOs) derived from induced pluripotent stem cells (hiPSC) assess: (1) expression main entry factors; (2) their vulnerability infection; (3) infection exposure transcriptome. Results proved that HCOs express receptors co‐receptors; may be productively infected by SARS‐CoV‐2; particles released SARS‐CoV‐2‐infected are able re‐infect another cellular line; (4) resulted in activation apoptotic stress pathways, along with inflammatory processes. Notably, these effects were recapitulated when exposed alone. The data obtained demonstrate likely infects probably through binding ACE2, CD147, NRP1 factors. Furthermore, alone sufficient disrupt homeostasis induce neurotoxic effects, potentially contributing onset long‐COVID symptoms.

Language: Английский

Citations

2
Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors DOI Creative Commons
Sarah Huff, Indrasena Reddy Kummetha, Shashi Kant Tiwari

et al.

Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 65(4), P. 2866 - 2879

Published: Sept. 27, 2021

The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify 2-phenyl-1,2-benzoselenazol-3-one class compounds targeting the SARS-CoV-2 main protease (Mpro). FRET-based screening against recombinant Mpro identified six that inhibit proteolysis with nanomolar IC50 values. Preincubation dilution experiments molecular docking determined inhibition can occur by either covalent or noncovalent mechanisms, lead E04 was to competitively. Lead E24 inhibited viral replication EC50 value (844 nM) in SARS-CoV-2-infected Vero E6 cells further confirmed impair human lung epithelial human-induced pluripotent stem cell-derived 3D organoids. Altogether, these studies provide structural framework mechanism should facilitate future treatments.

Language: Английский

Citations

90
Mechanisms of Antiviral Immune Evasion of SARS-CoV-2 DOI Open Access
Daniel K. Beyer, Adriana Forero

Journal of Molecular Biology, Journal Year: 2021, Volume and Issue: 434(6), P. 167265 - 167265

Published: Sept. 22, 2021

Language: Английский

Citations

89
Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation DOI Creative Commons
Shuai Xia, Qiaoshuai Lan, Yun Zhu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 29, 2021

Abstract The COVID-19 pandemic poses a global threat to public health and economy. continuously emerging SARS-CoV-2 variants present major challenge the development of antiviral agents vaccines. In this study, we identified that EK1 cholesterol-coupled derivative EK1, EK1C4, as pan-CoV fusion inhibitors, exhibit potent activity against infection in both lung- intestine-derived cell lines (Calu-3 Caco2, respectively). They are also effective pseudotyped B.1.1.7 (Alpha) B.1.1.248 (Gamma) well those with mutations S protein, including N417T, E484K, N501Y, D614G, which common South African Brazilian variants. Crystal structure revealed targets HR1 domain protein block virus-cell provide mechanistic insights into its broad activity. Nasal administration peptides hACE2 transgenic mice significantly reduced viral titers lung intestinal tissues. showed good safety profiles various animal models, supporting further clinical EK1-based inhibitors

Language: Английский

Citations

57
The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19 DOI Open Access
Shima Makaremi,

Ali Asgarzadeh,

Hamed Kianfar

et al.

Inflammation Research, Journal Year: 2022, Volume and Issue: 71(7-8), P. 923 - 947

Published: June 25, 2022

Language: Английский

Citations

53
Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids DOI Creative Commons
Jessica M. Vanslambrouck, Sean B. Wilson,

Ker Sin Tan

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 8, 2022

While pluripotent stem cell-derived kidney organoids are now being used to model renal disease, the proximal nephron remains immature with limited evidence for key functional solute channels. This may reflect early mispatterning of nephrogenic mesenchyme and/or insufficient maturation. Here we show that enhanced specification metanephric progenitors results in elongated and radially aligned proximalised nephrons distinct S1 - S3 tubule cell types. Such PT-enhanced possess improved albumin organic cation uptake, appropriate KIM-1 upregulation response cisplatin, expression SARS-CoV-2 entry factors resulting increased viral replication. The striking proximo-distal orientation resulted from localized WNT antagonism originating organoid stromal core. represent an study inherited acquired tubular disease as well drug responses.

Language: Английский

Citations

52