ABSTRACT
Introduction: Cangzhu, an herbal medicine used to treat symptoms of respiratory pneumonia in traditional Chinese medical system, has shown its effectiveness in combating fever, cough, and fatigue of current pandemic while no specialty drugs are available. Latest research in network pharmacology has confirmed the theoretical mechanism behind, the drug itself is commonly prescribed alone side another herb Aiye, which believed to be able to improve the effectiveness of Cangzhu. In this study, network pharmacology will be applied in search of potential mechanism behind. Method: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) is used to filter the active compounds and the target of the prescription compound. The Genecard and OMIM database are applied to identify the target related to our aim symptom fever, cough, and fatigue. The STRING database is used to analyse the intercepted targets. Compound-target interaction and protein-protein interaction networks are constructed using the Cytoscape between target disease Covid and our medicine mixture Cangzhu and Aiye. The Kyoto Encyclopaedia of Genes and Genome (KEGG) pathway and Gene Ontology (GO) enrichment analysis are performed for investigation of the molecular mechanisms. Finally, the interaction probability between the targets and the active compounds can be determined by molecular docking technology. Results: A total of 14 target are identified, in which are 10 most important targets and 2 key compounds. Besides, 216 biological processes items are obtained (P<0.05). Two hundred and seventy-one pathways are obtained (P<0.05). The result of molecular docking shows a stable binding between the active compounds and the target. Copyright © 2022 Textile Bioengineering and Informatics Society.
ABSTRACT
Stimulator of interferon genes, namely STING, an adaptor protein located in the endoplasmic reticulum, has been recognized as a shining target for cancer and infection research. However, STING agonists cyclic dinucleotides (CDNs) have shown almost zero efficacy in phase I clinical trials as a monotherapy, likely due to poor cellular permeability and rapid diffusion despite intratumoral injection. These deficiencies further affect other applications of CDNs, such as pandemic SARS-CoV-2 prevention and therapy. Here, we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene, namely CASTING (CAlixarene-STING), to improve CDN druggability, including degradation stability, cellular permeability, and tissue retention. CASTING efficiently enhances the immunostimulatory potency of CDG(SF) [a chemically modified cyclic di-GMP (CDG)] to generate an immunogenic microenvironment for melanoma regression, anti-PD-1 response rate increase, and durable memory formation against tumor recurrence. More importantly, CASTING displays a superior adjuvant activity on SARS-CoV-2 recombinant spike/receptor binding domain vaccines, inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo. Collectively, the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists. [GRAPHICS] .
ABSTRACT
Cangzhu is a Herbal medicine used to treat symptoms of respiratory diseases in Traditional Medicine system for hundreds of years and can be a new herbal solution for the current world pandemic. By using network pharmacology and molecular docking, this study explores the possible mechanisms of Cangzhu. One target is identified in the results. Further analysis identified 1 key target and 1 key compound. Moreover, 1052 biological processes, 61 cell compositions, and 124 molecular function items are obtained (P<0.05). One hundred and thirty pathways are obtained (P<0.05). The result of molecular docking shows a stable binding between the active compounds and the target. © 2019 Textile Bioengineering and Informatics Symposium Proceedings 2021 - 14th Textile Bioengineering and Informatics Symposium, TBIS 2021. All rights reserved.