ABSTRACT
Network pharmacology is a method to study the mechanism of a Traditional Chinese Medicine (TCM) prescription on a disease. However, most articles using network pharmacology to study the mechanism did not combine the weight information of herbs, the weight information of targets of disease, and the interaction information between targets together. We propose a method, network pharmacology combined with two iterations of PageRank algorithm, to make use of these information. It takes prescription-disease system as a whole, calculates PageRank score of targets in the prescription-disease system, which means an importance in the system, and the score is used to rank the analysis results of GO and KEGG pathway which help us to analyze the mechanism of a prescription on a disease. At last, we use two prescription-disease pairs which have been proved effectiveness in clinical trials: Qingfei Paidu Decoction on COVID-19, and FuFang DanShen Diwan on Coronary Heart Disease, and find that the results of our method are consistent with some results of clinical trials.Copyright © 2021
ABSTRACT
Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.
Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , COVID-19/therapy , CRISPR-Cas Systems , Gene Editing/methods , Gene Expression Regulation, Viral/genetics , RNA, Viral/analysis , SARS-CoV-2/genetics , Animals , Fluorometry/methods , Forecasting , Gene Knockout Techniques , High-Throughput Nucleotide Sequencing , Host-Pathogen Interactions , Humans , Mice , Mice, Transgenic , Models, Animal , Molecular Targeted Therapy , Nasopharynx/virology , Oropharynx/virology , RNA, Viral/genetics , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Sensitivity and SpecificityABSTRACT
BACKGROUND: At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. METHODS: First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein-protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. RESULTS: First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine-cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. CONCLUSIONS: DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.