论文标题

一种计算方法,用于帮助临床医生选择抗病毒药物的COVID-19试验

A computational approach to aid clinicians in selecting anti-viral drugs for COVID-19 trials

论文作者

Mongia, Aanchal, Saha, Sanjay Kr., Chouzenoux, Emilie, Majumdar, Angshul

论文摘要

COVID-19具有快速的药物重新定位以进行治疗。这项工作构建了相同的计算模型。目的是协助临床医生选择前瞻性抗病毒治疗的工具。由于已知该病毒会快速突变,因此该工具可能会帮助临床医生为突变分离株选择合适的抗病毒药物。 这项工作的主要贡献是公开共享的手动策划数据库,包括病毒及其相应抗病毒药之间的现有关联。数据库使用药物的化学结构和病毒的基因组结构收集相似性信息。除此数据库外,我们还可以根据矩阵完成提供一组最先进的计算药物重新定位工具。首先对工具进行了针对药物靶标相互作用的标准实验方案的分析。最佳性能的任务是重新定位Covid-19的抗病毒药的任务。这些工具选择了六种药物,其中四种目前处于各种试验阶段,即雷姆德西维尔(作为治愈方法),利巴巴林(与其他治愈方法结合使用),umifenovir(作为预防性和治愈方法)和sofosbuvir(作为治愈方法)。另一个一致的预测是Tenofovir alafenamide,这是一种新型的Tenofovir前药,以提高肾脏安全性,与对应的Tenofovir disoproxil相比。两者都在轨道下,前者是治愈的,后者是预防性的。这些结果表明,计算方法与练习状态同步。我们还展示了所选药物随着时间的推移而变突变,这表明这种工具在药物预测中的重要性。 该数据集和软件可在https://github.com/aanchalmongia/dva上公开获得,并且具有用户友好接口的预测工具可在http://dva.salsa.iiitd.edu.in.in上获得。

COVID-19 has fast-paced drug re-positioning for its treatment. This work builds computational models for the same. The aim is to assist clinicians with a tool for selecting prospective antiviral treatments. Since the virus is known to mutate fast, the tool is likely to help clinicians in selecting the right set of antivirals for the mutated isolate. The main contribution of this work is a manually curated database publicly shared, comprising of existing associations between viruses and their corresponding antivirals. The database gathers similarity information using the chemical structure of drugs and the genomic structure of viruses. Along with this database, we make available a set of state-of-the-art computational drug re-positioning tools based on matrix completion. The tools are first analysed on a standard set of experimental protocols for drug target interactions. The best performing ones are applied for the task of re-positioning antivirals for COVID-19. These tools select six drugs out of which four are currently under various stages of trial, namely Remdesivir (as a cure), Ribavarin (in combination with others for cure), Umifenovir (as a prophylactic and cure) and Sofosbuvir (as a cure). Another unanimous prediction is Tenofovir alafenamide, which is a novel tenofovir prodrug developed in order to improve renal safety when compared to the counterpart tenofovir disoproxil. Both are under trail, the former as a cure and the latter as a prophylactic. These results establish that the computational methods are in sync with the state-of-practice. We also demonstrate how the selected drugs change as the SARS-Cov-2 mutates over time, suggesting the importance of such a tool in drug prediction. The dataset and software is available publicly at https://github.com/aanchalMongia/DVA and the prediction tool with a user-friendly interface is available at http://dva.salsa.iiitd.edu.in.

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