A5045081364- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- Synthesis and biological activity
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Machine Learning in Materials Science
- RNA and protein synthesis mechanisms
- Hepatitis C virus research
- Biomedical Research and Pathophysiology
- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Signaling Pathways in Disease
- Tuberculosis Research and Epidemiology
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- Neuroblastoma Research and Treatments
- Synthesis and Characterization of Heterocyclic Compounds
- Protein Degradation and Inhibitors
- vaccines and immunoinformatics approaches
- COVID-19 Clinical Research Studies
ShanghaiTech University
2021-2025
Abstract Motivation The prediction of binding affinity between drug and target is crucial in discovery. However, the accuracy current methods still needs to be improved. On other hand, most deep learning focus only on non-covalent (non-bonded) molecular systems, but neglect cases covalent binding, which has gained increasing attention field development. Results In this work, a new attention-based model, A Transformer Encoder Fingerprint combined Prediction method for Drug–Target Affinity...
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection achieved penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors need be further revealed. shares similar sequences of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade either DPP4 or sialic acids. Sialic acids linked terminal...
3CLpro is an attractive target for the treatment of COVID-19. Using scaffold hopping strategy, we identified a potent inhibitor (3a) that contains thiocyanate moiety as novel warhead can form covalent bond with Cys145 protein. Tandem mass spectrometry (MS/MS) and X-ray crystallography confirmed mechanism formation between 3a protein in its catalytic pocket. Moreover, several analogues compound were designed synthesized. Among them, 3h shows best inhibition IC50 0.322 μM kinact/Ki value...
BACKGROUND: MAGT1 (magnesium transporter 1) is a subunit of the oligosaccharide protein complex with thiol-disulfide oxidoreductase activity, supporting process N-glycosylation. deficiency was detected in human patients X-linked immunodeficiency magnesium defect syndrome and congenital disorders glycosylation, resulting decreased cation responses lymphocytes, thereby inhibiting immune response against viral infections. Curative hematopoietic stem cell transplantation causes fatal bleeding...
Chimeric antigen receptor (CAR) T cells are powerful in eradicating hematological malignancies, but their efficacy is limited treating solid tumors. One of the barriers immunosuppressive response induced by immunomodulatory signaling pathways. Pharmacological targeting these pathways may be a simple way to improve CAR cells. In this study, anti-CD133 and anti-HER2 were generated from healthy donors, combination therapy using small molecules adenosine receptors was performed vitro vivo with...
Human society is facing the threat of various viruses. Proteases are promising targets for treatment viral infections. In this study, we collected and profiled 170 protease sequences from 125 viruses that infect humans. Approximately 73 them 3-chymotrypsin-like proteases (3CLpro), 11 pepsin-like aspartic (PAPs). Their sequences, structures, substrate characteristics were carefully analyzed to identify their conserved nature proposing a pan-3CLpro or pan-PAPs inhibitor design strategy. To...
Abstract Phenotypic drug discovery (PDD) screens compounds in cellular models that represent disease-relevant phenotypes, offering a compelling alternative to traditional target-based approaches. Unlike conventional methods, where act on single predefined target, PDD identifies capable of exerting therapeutic effects through multiple targets and mechanisms. This makes particularly valuable for discovering first-in-class drugs, especially diseases with poorly understood molecular mechanisms...
The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts canonical type IV exporter fold. Herein, we report structure unliganded Mtb IrtAB complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 3.5 Å. bound ATP-Mg2+ shows "head-to-tail" dimer nucleotide-binding domains (NBDs),...
Abstract The ATP-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis ( Mtb ), where its function is to import iron-loaded siderophores. Unusually, it adopts typical fold canonical ABC exporters. Here, we report structure unliganded IrtAB complex with ATP, ADP, an ATP analogue (AMP-PNP) at resolutions from 2.9 3.5 Å. In ATP-bound state, two nucleotide-binding domains (NBDs) form “head-to-tail” dimer, but has unexpectedly...
Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as adhesion thrombus growth. Although the blockade of GPVI function widely recognized potent anti-thrombotic approach, there are limited studies focused on site-specific targeting GPVI. Using computational modeling bioinformatics, we analyzed collagen- CRP-binding surfaces monomers dimers, compared interacting with other mammalian isoforms. We could predict minimal...
3C-like protease (3CLpro) is indispensable for the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rendering it to be a promising druggable target treating Corona Virus Disease 2019 (COVID-19). In this study, series 2,3,5-substituted [1,2,4]-thiadiazole analogs were discovered inhibit 3CLpro as non-peptidomimetic covalent binders at sub-micromolar levels, with IC50 values ranging from 0.118 0.582 µM. The antiviral abilities these compounds also...