A5070995929- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- Synthesis and biological activity
- Pharmacological Receptor Mechanisms and Effects
- Cytokine Signaling Pathways and Interactions
- T-cell and B-cell Immunology
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Phenothiazines and Benzothiazines Synthesis and Activities
- COVID-19 Clinical Research Studies
- Neuroscience and Neuropharmacology Research
- Click Chemistry and Applications
- Synthesis of Organic Compounds
- Phosphodiesterase function and regulation
- Neuropeptides and Animal Physiology
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Catalytic Reactions
- Synthesis and Biological Evaluation
- Biochemical and Molecular Research
- Cancer therapeutics and mechanisms
- HIV/AIDS drug development and treatment
- Essential Oils and Antimicrobial Activity
- Catalytic C–H Functionalization Methods
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
Shanghai Institute of Materia Medica
2016-2025
Chinese Academy of Sciences
2016-2025
University of Chinese Academy of Sciences
2019-2025
State Key Laboratory of Drug Research
2024
Hubei University of Technology
2024
La Trobe University
2014-2020
University of Nottingham
2013
Nanjing University
2009-2011
China Pharmaceutical University
2010
Zhejiang Pharmaceutical College
2007-2008
Abstract The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) urgently needs an effective cure. 3CL protease (3CL pro ) is a highly conserved cysteine proteinase that indispensable for replication, providing attractive target developing broad-spectrum antiviral drugs. Here we describe the discovery myricetin, flavonoid found in many food sources, as non-peptidomimetic and covalent inhibitor SARS-CoV-2 . Crystal structures...
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, origin excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like in vitro vivo. 2-E proteins were found form a type pH-sensitive cation channels bilayer lipid membranes. As observed SARS-CoV-2-infected cells, heterologous expression induced rapid cell death various susceptible...
The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) and its variants accentuates the great demand for developing effective therapeutic agents. Here, we report development an orally bioavailable SARS-CoV-2 3C-like protease (3CL
Abstract Background microRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. While number of known human and murine miRNAs is continuously increasing, information regarding from other species such as amphioxus remains limited. Results We combined Solexa sequencing with computational techniques to identify novel in B. belcheri (Gray). This approach allowed us 113 miRNA genes. Among them, 55 were conserved across encoded 45...
Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates protein–protein interaction (PPI) between catalytic subunit EZH2 EED. Deregulated PRC2 is intimately involved in tumorigenesis progression, making it an invaluable target for epigenetic cancer therapy. However, until now, there have been no reported small molecule compounds targeting EZH2-EED interactions. In...
SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CL
Abstract Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding herb–disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent multi-target and multi-component (MTMC) botanical therapeutics. Most existing prediction models fail incorporate MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction....
Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome 2 (SARS-CoV-2). We evaluated safety, tolerability, pharmacokinetics dose escalations simnotrelvir alone or with ritonavir (simnotrelvir simnotrelvir/ritonavir) healthy subjects, as well food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence...
The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself well psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence increased anxiety-like behavior in experimental autoimmune encephalomyelitis (EAE), accepted MS model. Due recently described critical role platelets inflammation disease, we examined relationship between platelets, inflammation, EAE. In elevated plus maze,...
Abstract The disassembly of apoptotic cells into small membrane-bound vesicles termed bodies (ApoBDs) is a hallmark apoptosis; however, the functional significance this process not well defined. We recently discovered new membrane protrusion (termed beaded apoptopodia) generated by monocytes which fragments to release an abundance ApoBDs. To investigate function monocyte disassembly, we used influenza A virus (IAV) infection as proof-of-concept model, IAV commonly infects in physiological...
Phosphodiesterase type 5 (PDE5) inhibitors are first-line therapy for pulmonary arterial hypertension (PAH) and erectile dysfunction. As a continuing work to improve the terminal half-lives oral bioavailabilities of our previously reported 4(3H)-pyrimidones, pharmacokinetics-driven optimization focusing on substituent is described. Two major congeneric series aminosulfonylphenylpyrimidones acylaminophenylpyrimidones, were designed, synthesized, pharmacologically assessed in vitro vivo. Among...
Cyclic nucleotide phosphodiesterase type 5 (PDE5) is a prime drug target for treating the diseases associated with lower level of cyclic guanosine monophosphate (cGMP), which specific substrate PDE5 hydrolysis. Here we report series novel inhibitors new scaffold monocyclic pyrimidin-4(3H)-one ring developed using structure-based discovery strategy. In total, 37 derivatives pyrimidin-4(3H)-ones, were designed, synthesized, and evaluated their inhibitory activities to PDE5, resulting in 25...
Abstract Memory regulatory T cells (mTregs) have been demonstrated to persist long‐term in hosts after the resolution of primary influenza A virus (IAV) infection. However, whether such IAV infection‐experienced (IAV‐experienced) mTregs differentiate into a phenotypically and functionally distinct Treg subset what function they play at infection site remains poorly defined. In this study, we characterized phenotype, examined responsiveness assessed suppressive IAV‐experienced memory Tregs...
Pulmonary arterial hypertension (PAH) is a devastating disease that can lead to right ventricular failure and premature death. Although approved drugs have been shown be safe effective, PAH remains severe clinical condition, the long-term survival of patients with still suboptimal. Thus, potential therapeutic targets new agents treat are urgently needed. In recent years, variety related pathways found, which brings hope for therapy. this perspective, not only marketed used summarized but...
Abstract Effective drugs with broad spectrum safety profile to all people are highly expected combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation nelfinavir could inhibit activity main protease (IC 50 = 8.26 μM), while its antiviral in Vero E6 cells a clinical isolate was determined be 2.93 μM (EC ). In comparison vehicle-treated animals, rhesus macaque...