A5055540928- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- Alzheimer's disease research and treatments
- Pancreatic function and diabetes
- Metal complexes synthesis and properties
- Viral gastroenteritis research and epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolism, Diabetes, and Cancer
- Biochemical and Molecular Research
- Drug Transport and Resistance Mechanisms
- HIV/AIDS drug development and treatment
- Crystal structures of chemical compounds
- Pain Mechanisms and Treatments
- Animal Virus Infections Studies
- Diabetes Treatment and Management
- Cholinesterase and Neurodegenerative Diseases
- HIV Research and Treatment
- Lanthanide and Transition Metal Complexes
- Malaria Research and Control
- Pharmacological Effects of Natural Compounds
- Sirtuins and Resveratrol in Medicine
- Helicobacter pylori-related gastroenterology studies
- Natural Antidiabetic Agents Studies
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
Nanjing University of Chinese Medicine
2017-2025
Shanghai Institute of Materia Medica
2011-2024
Chinese Academy of Sciences
2011-2024
University of Chinese Academy of Sciences
2016-2024
Xinjiang University
2024
China Pharmaceutical University
2022-2023
Soochow University
2022
First Affiliated Hospital of Soochow University
2022
University College London
2021
Royal Berkshire Hospital
2021
ABSTRACT The 3C-like proteinase (3CL pro ) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one the most promising targets for anti-SARS-CoV drugs due to its crucial role in viral life cycle. In this study, a database containing structural information more than 8,000 existing was virtually screened by docking approach identify potential binding molecules SARS-CoV 3CL . As target screening, both homology model and crystallographic structure pocket enzyme were used....
Diabetic peripheral neuropathy (DPN) is a common diabetic complication with no currently available curative treatments. Here, we demonstrated that the protein level of G-protein-coupled receptor 40 (GPR40) significantly repressed in sciatic nerves (SN) DPN patients, as well nerves, including dorsal root ganglia (DRG) and SN, streptozotocin (STZ)-induced type 1 mice BKS Cg-m+/+Lepr db/J (db/db) 2 mice. We identified amlodipine besylate (AB), first-line clinical antihypertensive drug, GPR40...
The nucleocapsid (N) protein of SARS coronavirus (SARS_CoV) is a major structural component virions, which appears to be multifunctional involved in viral RNA replication and translation. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) related the pre‐mRNA splicing nucleus translation regulation cytoplasm. In this report, based on relevant biophysical biochemical assays, SARS_CoV (SARS_N) was discovered exhibit high binding affinity human hnRNP A1. GST pull‐down results clearly...
Malaria is caused by protozoan erythrocytic parasites of the Plasmodium genus, with falciparum being most dangerous and widespread disease-causing species. Falcipain-2 (FP-2) P. a papain-family (C1A) cysteine protease that plays an important role in parasite life cycle degrading erythrocyte proteins, notably hemoglobin. Inhibition FP-2 its paralogues prevents maturation, suggesting these proteins may be valuable targets for design novel antimalarial drugs, but lack structural knowledge has...
β-Secretase (β-site amyloid precursor protein-cleaving enzyme 1; BACE1) is a transmembrane aspartic protease that cleaves the β-amyloid protein en route to generation of β-peptide (Aβ) believed be responsible for Alzheimer's disease cascade. It thus prime target development inhibitors which may serve as drugs in treatment and/or prevention disease. In following determination crystal structures both apo and complexed BACE1, structural analysis all BACE1 deposited PDB molecular dynamics (MD)...
Abstract Alzheimer's disease (AD) is a progressively neurodegenerative characterized by cognitive deficits and alteration of personality behavior. As yet, there no efficient treatment for AD. 5HT 2A receptor (5HT R) subtype 2 belonging to the serotonin family, its antagonists have been clinically used as antipsychotics relieve psychopathy. Here, we discovered that first‐line antiallergic drug desloratadine (DLT) functioned selective antagonist R efficiently ameliorated pathology APP/PS1...
Background & AimsThe ligand-activated transcription factor, aryl hydrocarbon receptor (AHR) can sense xenobiotics, dietary, microbial, and metabolic cues. Roles of Ahr in intestinal epithelial cells (IECs) have been much less elucidated compared with those innate immune cells. Here, we explored whether the IEC intrinsic could modulate development alcohol-related liver disease (ALD) via gut–liver axis.MethodsMice specific deficiency (AhrΔIEC) were generated fed a control or ethanol diet....
The nucleocapsid (N) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) is a major virion structural protein. In this study, two epitopes (N1 and N2) the N SARS-CoV were predicted by bioinformatics analysis. After immunization with peptides, peptides-specific antibodies isolated from immunized rabbits. further experiments demonstrated that N1 peptide-induced polyclonal had high affinity to bind E. coli expressed SARS-CoV. Furthermore, it was confirmed peptide-specific IgG...
Severe acute respiratory syndrome (SARS) coronavirus is a novel human and responsible for SARS infection. 3C-like proteinase (SARS 3CL(pro)) plays key roles in viral replication transcription an attractive target anti-SARS drug discovery. In this report, we quantitatively characterized the dimerization features of full-length N-terminal residues 1-7 deleted 3CL(pro)s by using glutaraldehyde cross-linking SDS-PAGE, size-exclusion chromatography, isothermal titration calorimeter techniques....
Coronavirus nucleocapsid (N) protein envelops the genomic RNA to form long helical during virion assembly. Since N oligomerization is usually a crucial step in this process, characterization of such an will help understanding possible mechanisms for formation. The severe acute respiratory syndrome coronavirus (SARS-CoV) was recently discovered self-associate by its carboxyl terminus. In study, further address detailed association feature C-terminus, systematically investigated size exclusion...
3C-like protease (3CL pro) plays pivotal roles in the life cycle of severe acute respiratory syndrome coronavirus (SARS-CoV) and only dimeric is proposed as functional form. Guided by crystal structure molecular dynamics simulations, we performed systematic mutation analyses to identify residues critical for 3CL pro dimerization activity this study. Seven on dimer interface were selected evaluating their contributions stability catalytic biophysical biochemical methods. These are involved...
We described a prospective application of ligand-based virtual screening program SHAFTS to discover novel inhibitors for p90 ribosomal S6 protein kinase 2 (RSK2). Taking the putative 3D conformations two weakly binding RSK2 NTKD as query templates, was used perform similarity based because lack crystal structure protein, thus leading identification several scaffolds that would have been missed by conventional 2D fingerprint methods. The most potent hit compounds show low micromolar...
Cardiac fibrosis is a deleterious consequence of hypertension which may further advance to heart failure and increased matrix metalloproteinase-9 (MMP-9) contributes the underlying mechanism. Therefore, new therapeutic strategies attenuate effects MMP-9 are urgently needed. In present study, we characterize salvianolic acid A (SalA) as novel inhibitor at molecular, cellular animal level. We expressed truncated form contains only catalytic domain (MMP-9 CD), used this active protein for...
Nuclear receptors retinoic X receptor α (RXRα) and peroxisome proliferator activated γ (PPARγ) function potently in metabolic diseases, are both important targets for anti-diabetic drugs. Coactivation of RXRα PPARγ is believed to synergize their effects on glucose lipid metabolism. Here we identify the natural product magnolol as a dual agonist targeting PPARγ. Magnolol was previously reported enhance adipocyte differentiation uptake, ameliorate blood level prevent development diabetic...
Farnesoid X receptor α (FXRα) as a bile acid sensor plays potent roles in multiple metabolic processes, and its antagonist has recently revealed special interests the treatment of disorders, although underlying mechanisms still remain unclear. Here, we identified that small molecule N-benzyl-N-(3-(tert-butyl)-4-hydroxyphenyl)-2,6-dichloro-4-(dimethylamino) benzamide (NDB) functioned selective human FXRα (hFXRα), crystal structure hFXRα ligand binding domain (hFXRα-LBD) complex with NDB was...
Hepatic stellate cell (HSC) activation induced by transforming growth factor β1 (TGF-β1) plays a pivotal role in fibrogenesis, while the complex downstream mediators of TGF-β1 such process are largely unknown.We performed pharmacoproteomic profiling mice liver tissues from control, carbon tetrachloride (CCl4)-induced fibrosis and NPLC0393 administrated groups. The target gene MAT2A was overexpressed or knocked down vivo tail vein injection AAV vectors. We examined NF-κB transcriptional...