相关实验视频

Updated: May 30, 2025

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

一个基于基因的计算药物重定向框架,用于快速识别候选化合物:应用于COVID-19

Georgios Voloudakis^{1,2,3,4,5,6,7}, Kyung Min Lee⁸, James M Vicari^1,2,3,4

¹Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY USA.

medRxiv : the preprint server for health sciences

|January 27, 2025

概括

这项研究使用了计算药物重定向框架,整合了基因表达和电子健康记录,以确定潜在的COVID-19治疗方法. 阿扎西奥普林和视网醇显示COVID-19发病率降低,而内尔菲纳维尔和萨基纳维尔在体外抑制了SARS-CoV-2.

科学领域:

计算生物学是一种计算生物学.
药理学药理学是指药理学的学科.
传染病研究传染病研究.

背景情况:

药物开发是耗时和昂贵的.
计算药物重定向可以加快对现有药物的新用途的识别.
验证计算预测仍然是一个重大挑战.

研究的目的:

使用基因调节基因表达 (GReX) 和电子病历 (EMR) 数据进行药物重定向框架的基准测试.
识别与减少COVID-19发病率和SARS-CoV-2抑制相关的FDA批准的药物.
通过体内和体外验证来评估计算预测的有效性.

主要方法:

一个基于5个方法级别的计算药物优先级管道,集成多组织GReX和药物转录签名.
优先考虑FDA批准的药物,并评估它们与退伍军人卫生管理局 (VHA) 队列中COVID-19发病率的关联.
在实验室评估人类肺上皮细胞中SARS-CoV-2复制抑制对选定的候选药物.

主要成果:

通过in silico管道,七种FDA批准的药物被确定为前十名候选药物.
阿扎西奥普林和视网醇与VHA队列中的COVID-19发病率降低显著相关.
奈尔菲纳维尔和萨基纳维尔在体外表现出强大的SARS-CoV-2抑制作用,但没有任何单一化合物在体外和体外环境中表现出强大的保护作用.

结论:

基于GReX的药物重定向有效地识别了具有潜在临床相关性的现有疗法.
结合流行病学数据和体外试验的补充性验证方法可以完善有前途的候选药物.
这种综合验证策略可以加速对当前和未来的健康挑战的治疗开发.

关键词:

在 COVID-19 疫情中,在TWAS中,TWAS就是TWAS.计算性药物重定向使用药学流行病学药学流行病学

更多相关视频

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses

Published on: May 5, 2014

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

相关概念视频

Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Structure-Activity Relationships and Drug Design

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...

G Protein-coupled Receptors

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...