A5101902216- Adipose Tissue and Metabolism
- Hepatitis B Virus Studies
- HIV Research and Treatment
- Genomics, phytochemicals, and oxidative stress
- Hepatitis C virus research
- Erythrocyte Function and Pathophysiology
- Mosquito-borne diseases and control
- Lipid metabolism and biosynthesis
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Insect symbiosis and bacterial influences
- Peroxisome Proliferator-Activated Receptors
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Hemoglobinopathies and Related Disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer, Hypoxia, and Metabolism
- Signaling Pathways in Disease
- Biochemical and Molecular Research
- SARS-CoV-2 detection and testing
- Acute Kidney Injury Research
- Protein Interaction Studies and Fluorescence Analysis
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Exercise and Physiological Responses
China Medical University
2019-2024
Ministry of Education of the People's Republic of China
2023
Janssen (United States)
2017
Guangzhou Blood Center
2003-2016
Academy of Military Medical Sciences
2015
Roche (Switzerland)
2010
University at Albany, State University of New York
2007-2008
New York State Department of Health
2007
Wadsworth Center
2007
State University of New York
1993
ABSTRACT The plus-strand RNA genome of flavivirus contains a 5′ terminal cap 1 structure (m 7 GpppAmG). flaviviruses encode one methyltransferase, located at the N-terminal portion NS5 protein, to catalyze both guanine N-7 and ribose 2′-OH methylations during viral formation. Representative methyltransferases from dengue, yellow fever, West Nile virus (WNV) sequentially generate GpppA → m GpppAm. 2′-O methylation can be uncoupled methylation, since GpppA-RNA readily methylated GpppAm-RNA....
The hepatitis B virus (HBV) core protein is essential for HBV replication and an important target antiviral drug discovery. We report the first, to our knowledge, high-resolution crystal structure of compound bound protein. NVR-010-001-E2 can induce assembly wild-type Y132A mutant proteins thermostabilize with a Tm increase more than 10 °C. binds at dimer-dimer interface proteins, forms new interaction surface promoting protein-protein interaction, induces assembly, increases stability....
The hepatitis B virus (HBV) core protein serves multiple essential functions in the viral life cycle, and antiviral agents that target are being developed. Capsid assembly modulators (CAMs) compounds misdirect capsid assembly, resulting suppression of HBV replication virion production. Besides DNA, circulating RNA has been detected patient serum can be associated with treatment response. Here we studied effect CAMs on production extracellular using infected HepaRG cells primary human...
The 5' end of the flavivirus plus-sense RNA genome contains a type 1 cap (m(7)GpppAmG), followed by conserved stem-loop structure. We report that nonstructural protein 5 (NS5) from four serocomplexes flaviviruses specifically methylates through recognition terminus viral RNA. Distinct elements are required for methylations at guanine N-7 on and ribose 2'-OH first transcribed nucleotide. In West Nile virus (WNV) model, methylation requires specific nucleotides second third positions...
ABSTRACT Flaviviruses encode a single methyltransferase domain that sequentially catalyzes two methylations of the viral RNA cap, GpppA-RNA→m 7 GpppAm-RNA, by using S -adenosyl- l -methionine (SAM) as methyl donor. Crystal structures flavivirus methyltransferases exhibit distinct binding sites for SAM, GTP, and molecules. Biochemical analysis West Nile virus shows SAM-binding site donates groups to both N7 2′-O positions GTP-binding pocket functions only during methylation, sets amino acids...
NVR 3-778 is the first capsid assembly modulator (CAM) that has demonstrated antiviral activity in hepatitis B virus (HBV)-infected patients. inhibited generation of infectious HBV DNA-containing particles with a mean 50% effective concentration (EC50) 0.40 µM HepG2.2.15 cells. The profile indicates pan-genotypic and lack cross-resistance nucleos(t)ide inhibitors replication. combination analogs vitro resulted additive or synergistic activity. Mutations within hydrophobic pocket at...
Nuclear factor erythroid 2-related 1 (NRF1), a ubiquitously expressed CNC-bZIP transcription factor, plays critical role in white adipocyte (WAC) biology, whereas the underlying mechanisms remain unknown. The mouse Nrf1 gene is transcribed number of alternatively spliced forms, resulting two long protein isoforms (L-NRF1) containing 741 and 742 amino acids (aa) multiple short (S-NRF1). Our previous study found that adipocyte-specific knockout [Nrf1(f)-KO] mice disturbs expression lipolytic...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19 pandemic that began in 2019. The 3-chymotrypsin-like cysteine protease (3CLpro) controls replication and therefore considered a major target for antiviral discovery. This study describes evaluation SARS-CoV-2 3CLpro inhibitors novel self-assembled monolayer desorption ionization mass spectrometry (SAMDI-MS) enzymatic assay. Compared with traditional FRET readout, label-free SAMDI-MS assay offers greater...
Pancreatic cancer is a fatal human malignancy associated with an exceptionally poor prognosis. Novel therapeutic strategies are urgently required to treat this disease. In addition immunosuppressive activity, triptolide possesses strong antitumor activity and synergistically enhances the activities of conventional chemotherapeutic drugs in preclinical models pancreatic cancer. The present study investigated effects cells, either combination gemcitabine, or alone. BxPC-3 PANC-1 cell lines...
A functional cure of chronic hepatitis B requires eliminating the virus (HBV)-encoded surface antigen (HBsAg), which can suppress immune responses. STOPS are phosphorothioated single-stranded oligonucleotides containing novel chemistries that significantly reduce HBsAgs produced by HBV-infected liver cells. The molecule ALG-10000 functions inside cells to levels multiple HBV-encoded molecules. However, it does not bind HBV An affinity resin coupled with was found several proteins from...
Fine-tuning of osteoclast differentiation (OD) and bone remodeling is crucial for homeostasis. Dissecting the mechanisms regulating osteoclastogenesis fundamental to understanding pathogenesis various disorders including osteoporosis arthritis. Nuclear factor erythroid 2-related 1 (NFE2L1, also known as NRF1), which belongs CNC-bZIP family transcription factors, orchestrates a variety physiological processes stress responses. While Nfe2l1 gene may be transcribed into multiple alternatively...
Radiation-induced intestinal injury is a common complication in radiotherapy for solid organ malignancies abdomen or pelvis. However, currently there are no approved medical countermeasures radiation-induced injury. Therefore, it urgent to develop new treatments In the present study, we demonstrated that bone marrow derived mesenchymal stem cells (MSCs) and overexpression of human manganese superoxide dismutase (MnSOD) could ameliorate syndrome. NOD/SCID mice received abdominal irradiation...
Brown adipose tissue (BAT) is a major site of non-shivering thermogenesis in mammals and plays an important role energy homeostasis. Nuclear factor-erythroid 2-related factor 1 (NFE2L1, also known as Nrf1), master regulator cellular metabolic homeostasis numerous stress responses, has been found to function critical driver BAT thermogenic adaption cold or obesity by providing proteometabolic quality control. Our recent studies using adipocyte-specific Nfe2l1 knockout [Nfe2l1(f)-KO] mice...
It has been hypothesized that the cytosolic esterase-induced fluorescence intensity (CEIFI) from carboxy dimethyl fluorescein diacetate (CMFDA) in platelets may related to platelet functions. In present study, we measured change of CEIFI during storage, and examined correlations with vitro functionality stored platelets, including ADP-induced aggregation activity, hypotonic shock response, expression CD62P as well apoptosis. The fresh when tested at 10 μM CMFDA, mean index (MFI) was 305.9 ±...
Abstract There is an urgent need for antivirals targeting the SARS-CoV-2 virus to fight current COVID-19 pandemic. The main protease (3CLpro) represents a promising target antiviral therapy. lack of selectivity some reported 3CLpro inhibitors, specifically versus cathepsin L, raises potential safety and efficacy concerns. ALG-097111 potently inhibited (IC 50 = 7 nM) without affecting activity human L > 10 μM). When was dosed in hamsters challenged with SARS-CoV-2, robust significant 3.5...