A5050005779- Hepatitis C virus research
- Viral Infections and Immunology Research
- Liver physiology and pathology
- Hippo pathway signaling and YAP/TAZ
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
- HIV/AIDS drug development and treatment
- Signaling Pathways in Disease
- Animal Disease Management and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Liver Disease and Transplantation
- RNA regulation and disease
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Catalytic C–H Functionalization Methods
- Glycosylation and Glycoproteins Research
- Quinazolinone synthesis and applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Protein purification and stability
- Phagocytosis and Immune Regulation
- Galectins and Cancer Biology
- Endoplasmic Reticulum Stress and Disease
Tsinghua University
2013-2025
Southwest Medical University
2020-2025
Sichuan University
2020-2021
State Key Laboratory of Biotherapy
2020-2021
Center for Life Sciences
2013-2016
Indiana University School of Medicine
2014
Liver fibrosis, one of the main histological determinants various chronic liver diseases, currently lacks effective treatment. Hepatic stellate cells (HSCs) are pivotal in production extracellular matrix and amplify fibrogenic response. Inhibiting activation HSCs or promoting senescence activated is crucial for regression fibrosis. The ATPase p97, also known as valosin-containing protein (VCP), a central component ubiquitin-proteasome system, it regulates numerous cellular processes by...
Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 We demonstrated that CypA played an essential role entry and RNA interference-mediated reduction endogenous expression led to decreased multiplication. further revealed directly interacted modified conformation...
The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe discovery novel potent HCV inhibitors by employing a virtual screening (VS) approach, which based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In RB-VS stage, after feature selection, model with 16 descriptors was used. PB-VS six energy-based pharmacophore (e-pharmacophore) models from different crystal structures...
ABSTRACT Enterovirus 71 (EV71) ( Picornaviridae family) and hepatitis C virus (HCV) Flaviviridae are the causative agents of human hand, foot, mouth disease (HFMD) C, resulting in a severe pandemic involving millions infections Asia-Pacific region worldwide. The great impact EV71 HCV on public health highlights need to further our understanding biology these two viruses develop effective therapeutic antivirals. Here, we evaluated total 32 lycorine derivatives demonstrated that...
Neuroinflammation is a critical mechanism responsible for the progression of Alzheimer's disease (AD). Recent studies reveal that Hippo/Yes-associated protein (YAP) signaling pathway highly associated with series inflammation-related disorders. Glial cell line-derived neurotrophic factor (GDNF), its and anti-apoptotic functions nervous system, has been demonstrated to decrease expression proinflammatory mediators. Here we investigated whether Hippo/YAP may affect amyloid-β (Aβ)-induced...
RO8191 represents a newly identified small-molecule IFN-α-substitute, which displays potent anti-HCV activity. In this communication, we reported the design and synthesis of two series imidazo[1,2-α][1,8]naphthyridine derivatives, as analogues, via direct C-H arylation approach. Notably, by adjusting reaction conditions, could achieve analogues regioselective single- double-arylations, respectively. The activities synthesized compounds were evaluated within HCV cell culture system,...
Kidney fibrosis is accompanied by vascular dysfunction. Discovering new ways to ameliorate dysfunctional angiogenesis may bypass kidney fibrosis. YAP (Yes-associated protein) plays a multifaceted role during angiogenesis. Here, we found that selectively targeting signaling in the endothelium ameliorates unilateral ureteral obstruction (UUO)-induced Genetic deletion of Yap1, encoding protein, VE-cadherin+ endothelial cells inhibited endothelial-to-mesenchymal transition (EndMT) and improved...
The pandemic of acute respiratory disease in 2019 caused by highly pathogenic and infectious SARS-CoV-2 has seriously endangered human public safety. 6-HB (HR1–HR2 complex) formation occurring the process spike protein-mediated membrane fusion could serve as a conserved potential target for design inhibitors. Based on HR2 domain 6-HB, we designed synthesized 32 stapled peptides using an all-hydrocarbon peptide stapling strategy. Owing to improved proteolytic stability higher helical...
RO8191 represents a newly discovered small-molecule IFN-like agent that displays potent anti-HCV activity. With it as lead, series of compounds bearing an imidazo[1,2-α][1,8]naphthyridine core and amide bond-linked side chain were designed synthesized. These evaluated on HCV cell culture system (HCVcc-hRluc-JFH1), some them exhibited remarkable activity (EC50 = 0.017–0.159 μM) low toxicity (CC50 > 25 μM). Moreover, was revealed these identified agents exert their antiviral effect through...
In this work, the relationship between cyclophilin A (CypA) and HCV prompted us to screen a series of small molecule CypA inhibitors which were previously reported by our group. Among them, compound 1, discovered as non-immunosuppressive anti-HCV agent with an EC50 value 0.67 μM in virus assay, was selected for further study. Subsequent chemical modification O-acylation led novel class molecules, among 25 demonstrated most potent activity assay (EC50 = 0.19 μM), but low cytotoxicity hERG...
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination antivirals targeting multiple processes lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry an essential target step for antiviral development, but FDA-approved inhibitor remains exclusive. Here we identify serotonin 2A receptor (5-HT2AR) factor amendable to therapeutic...
We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has binding affinity 16 nM for SARS-CoV-2 spike RBD, effectively inhibits pseudovirus in Huh7-hACE2 cells with an IC50 190 neutralizes authentic Caco2 2.4 μM. Our study should provide new insight optimization peptide-based anti-SARS-CoV-2 inhibitors.
Upon sensing pathogen-associated patterns and secreting interferons (IFNs) into the environment, host cells perceive extracellular type I IFNs by IFNα/β receptors IFNAR1 IFNAR2 to stimulate downstream innate immune signaling cascades. Through use of chemical probes, we demonstrated that facilitates hepatitis C virus (HCV) entry. Silencing significantly attenuated HCV proliferation. binds infectious virions through a direct interaction its D2 domain with C-terminal end apolipoprotein E (apoE)...
Cholestatic fibrogenesis is a pathobiological process in which cumulative injury to the bile ducts coincides with progressive liver fibrosis. The pathobiologic mechanisms underlying and disease progression remain poorly understood. Currently, there no effective treatment for In this study, we discovered that components of coagulation cascade were associated advanced obstructive cholestasis, anticoagulant therapy could improve cholestasis-induced mouse model common duct ligation (BDL), mimics...
The antibody response plays a crucial role against hepatitis C virus (HCV) infection, and our understanding of this intricate progress in vivo is far from complete. We previously reported novel robust technique based on large combinatorial viral antigen library displayed the surface yeast Saccharomyces cerevisiae, allowing comprehensive profiling polyclonal responses both qualitative quantitative terms. Here, we report generation application HCV strain JFH1 envelope glycoprotein to profile...
In recent years, hand-foot-and-mouth disease (HFMD), which is caused by Enteroviruses, has emerged as a serious illness.It affects mainly children under the age of five and results in high fatality rates.Enterovirus 71 (EV71) main causative agent HFMD China currently there are no effective anti-viral drugs available to treat HFMD.In present study, we screened compounds for inhibition proliferation EV71.Compound YZ-LY-0 stalled life cycle EV71.The inhibitor exhibited EC 50 value 0.29 μm...