A5088699320- Computational Drug Discovery Methods
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- Hepatitis C virus research
- Machine Learning in Materials Science
- Biomedical Text Mining and Ontologies
- Chronic Lymphocytic Leukemia Research
- Metabolomics and Mass Spectrometry Studies
- Bioinformatics and Genomic Networks
- Microbial Natural Products and Biosynthesis
- PI3K/AKT/mTOR signaling in cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Metabolism and Genetic Disorders
- Chemical Synthesis and Analysis
- Inflammasome and immune disorders
- Microbial Metabolic Engineering and Bioproduction
- Immunodeficiency and Autoimmune Disorders
- Fluorine in Organic Chemistry
- Viral Infectious Diseases and Gene Expression in Insects
- Toxin Mechanisms and Immunotoxins
- Animal Virus Infections Studies
- Infectious Encephalopathies and Encephalitis
- Cytokine Signaling Pathways and Interactions
- Genetics, Bioinformatics, and Biomedical Research
East China University of Science and Technology
2018-2025
East China Normal University
2023
Shanghai East Hospital
2021
ORCID
2020
Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics pandemics worldwide, such as the on-going outbreak of novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors human DHODH, S312 S416, with favorable drug-likeness pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various viruses, including influenza A virus, Zika Ebola particularly Notably, S416 is reported to be most inhibitor so far an EC 50 17 nmol/L SI value...
Drug discovery and development affects various aspects of human health dramatically impacts the pharmaceutical market. However, investments in a new drug often go unrewarded due to long complex process research (R&D). With advancement experimental technology computer hardware, artificial intelligence (AI) has recently emerged as leading tool analyzing abundant high-dimensional data. Explosive growth size biomedical data provides advantages applying AI all stages R&D. Driven by big...
Large-scale COVID-19 vaccinations are currently underway in many countries response to the pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, renal functions healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported patients, suggesting that mimicked infection. Single-cell mRNA sequencing (scRNA-seq) peripheral blood...
Bruton's tyrosine kinase (BTK) is a therapeutic target for B-cell-driven malignancies. Most of the approved covalent BTK inhibitors are associated with treatment limitations due to off-target toxicity and drug resistance. Developing noncovalent promising strategy address unmet clinical needs. Here, novel series pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives were designed synthesized as inhibitors. Among them, representative compound 9 exhibited potent inhibitory activity (IC50 = 21.6 nM)...
Water molecules play an important role in modeling protein-ligand interactions. However, traditional molecular docking methods often ignore the impact of water by removing them without any analysis or keeping as a static part proteins ligands. Hence, accuracy simulations will inevitably be damaged. Here, we introduce multi-body program which incorporates fixed variable number key simulations. The employed NSGA II, multi-objective optimization algorithm, to identify binding poses ligand and...
Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics pandemics worldwide, such as the on-going outbreak of coronavirus SARS-CoV-2. Existing direct-acting antiviral (DAA) drugs cannot be applied immediately to new because virus-specificity, development DAA from beginning is not timely for outbreaks. Thus, host-targeting (HTA) have many advantages fight against a broad spectrum viruses, by blocking viral replication overcoming potential mutagenesis simultaneously. Herein,...
Drug metabolism research plays a key role in the discovery and development of drugs. Based on drug metabolites, new chemical entities can be identified potential safety hazards caused by reactive or toxic metabolites minimized. Nowadays, computational methods are usually complementary tools for experiments. However, current prediction tend to have high false positive rates with low accuracy only used specific enzyme systems. In order overcome this difficulty, method was developed paper first...
Construction of high-quality fragment libraries by segmenting organic compounds is an important part the drug discovery paradigm. This article presents a new method, MacFrag, for efficient molecule fragmentation. MacFrag utilized modified version BRICS rules to break chemical bonds and introduced subgraphs extraction algorithm rapid enumeration space. The evaluation results with ChEMBL dataset exhibited that was overall faster than implemented in RDKit molBLOCKS. Meanwhile, fragments...
Natural products (NPs), as a vital source of pharmaceutical agents, have contributed to the development 60% marketed small-molecule drugs. However, NP-based drug discovery faces major challenge due combinatorial expansion NPs' configurational space and their complex 3D-structures, which arise from atomic chirality dictated by stereospecific biosynthetic enzymes. To date, over 20% known NPs lack complete chiral configuration annotations, only 1–2% fully resolved crystal structures. address...
Identification of new chemical compounds with desired structural diversity and biological properties plays an essential role in drug discovery, yet the construction such a potential space elements 'near-drug' is still challenging task. In this work, we proposed multimodal information reconstruction system to automatically process, extract align heterogeneous from text descriptions images patents. Our key innovation lies data generator that produces cross-modality training form Markush...
Molecular docking aims to predict possible drug candidates for many diseases, and it is computationally intensive. Particularly, in simulating the ligand-receptor binding process, pocket of receptor divided into subcubes, when ligand docked all cubes, there are molecular tasks, which extremely time-consuming. In this study, we propose a heterogeneous parallel scheme process accelerate simulating. The includes two layers parallelism, coarse-grained layer parallelism implemented...
Bruton's tyrosine kinase (BTK) is an attractive therapeutic target in the treatment of cancer, inflammation, and autoimmune diseases. Covalent noncovalent BTK inhibitors have been developed, among which covalent shown great clinical efficacy. However, some them could produce adverse effects, such as diarrhea, rash, platelet dysfunction, are associated with off-target inhibition ITK EGFR. In this study, we disclosed a series pteridine-7(8H)-one derivatives potent selective inhibitors, were...
Target discovery and identification processes are driven by the increasing amount of biomedical data. The vast numbers unstructured texts publications provide a rich source knowledge for drug target research demand development specific algorithms or tools to facilitate finding disease genes proteins. Text mining is method that can automatically mine helpful information related from massive literature. However, there substantial lag between subsequent abstraction extracted text databases....
Comprehensive Summary The binding of Sphingosine‐1‐phosphate (S1P) with the S1PR1‐5 plays a fundamental physiological role in number processes including vascular development and stabilization, lymphocyte migration distribution. S1P‐S1PR1 signal axis established roles immune cell trafficking thus playing therapeutic multiple sclerosis inflammatory bowel disease. In this study, series oxadiazole derivatives were designed synthesized as S1PR1 agonists based on rational drug design. Among them,...
Summary of main observation and conclusion Macrocycle has attracted the attention many researchers in field medicinal chemistry due to its unique advantages good prospects, but difficulties drug design synthesis macrocycle limit applications. In this study, a series macrocyclic derivatives designed from anaplastic lymphoma kinase (ALK) inhibitor lorlatinib were synthesized as Janus 2 (JAK2) selective inhibitors. Among them, 17f had best inhibitory activity (IC 50 = 0.177 μmol·L –1 )...
Abstract Protein kinases are central mediators of signal-transduction cascades and attractive drug targets for therapeutic intervention. Since structurally mechanistically related to each other, kinase inhibitor selectivity is often investigated by profiling considered as an important index discovery. We here describe a versatile web server termed ProfKin structure-based profiling, which based on kinase-ligand focused database (KinLigDB). It provides all ready-to-use 3D structure coordinates...
In the original publication there are few errors in Figure 1. The correct 1 is provided this correction