相关实验视频

Updated: Jun 30, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

药物耐药性预测基于一个定向的旗变压器

Dong Chen, Gengzhuo Liu, Hongyan Du

|March 18, 2024

概括

一个名为CAPTURE的新工具通过分析主要蛋白酶 (Mpro) 中的突变来预测SARS-CoV-2的耐药性. 它确定了已知的和潜在的抗药性突变,帮助开发下一代治疗方法.

科学领域:

病毒学病毒学
药物发现药物发现药物发现
计算生物学计算生物学

背景情况:

随着SARS-CoV-2的演变,全球卫生面临着挑战,而耐药性则是一个主要问题.
抗病毒药物PAXLOVID向病毒主要蛋白酶 (Mpro),突变可以赋予抗性.

研究的目的:

开发一个计算框架,CAPTURE,用于预测SARS-CoV-2耐药性突变.
分析Mpro突变对尼尔马特雷尔维尔结合 afinity 的影响,并确定潜在的抗性驱动变体.

主要方法:

开发了CAPTURE,将突变分析与抗性预测模块 (DFFormer-seq) 集成在一起.
使用定向旗变压器和从蛋白质和小分子-大语言模型中嵌入序列.
分析了Mpro突变频率和与nirmatrelvir.vir的结合亲缘关系.

主要成果:

观察到Mpro结合部位附近的突变频率增加,这表明PAXLOVID的选择性压力.
确定了经过实验确认的耐药性突变 (H172Y,F140L) 和五种新的潜在突变.
在测试数据集上预测耐药突变时,获得了57%的回忆率和71%的精度.

结论:

CAPTURE为预测耐药性和实时病毒监测提供了一个强大的框架.
这些发现指导了下一代抗病毒疗法针对SARS-CoV-2的合理设计.
突出了抗病毒药物的选择性压力对病毒进化的影响.

更多相关视频

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

QTL Mapping and CRISPR/Cas9 Editing to Identify a Drug Resistance Gene in Toxoplasma gondii

QTL Mapping and CRISPR/Cas9 Editing to Identify a Drug Resistance Gene in Toxoplasma gondii

Published on: June 22, 2017

相关概念视频

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

Antibiotic Selection

Antibiotic Selection