Institute for Systems Analysis and Computer Science, Antonio Ruberti", National Research Council, Rome, Italy.
Fondazione Per La Medicina Personalizzata, Via Goffredo Mameli, 3/1, Genoa, Italy.
BMC Bioinformatics. 2021 Mar 23;22(1):150. doi: 10.1186/s12859-021-04076-w.
Currently, no proven effective drugs for the novel coronavirus disease COVID-19 exist and despite widespread vaccination campaigns, we are far short from herd immunity. The number of people who are still vulnerable to the virus is too high to hamper new outbreaks, leading a compelling need to find new therapeutic options devoted to combat SARS-CoV-2 infection. Drug repurposing represents an effective drug discovery strategy from existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery.
We developed a network-based tool for drug repurposing provided as a freely available R-code, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), with the aim to offer a promising framework to efficiently detect putative novel indications for currently marketed drugs against diseases of interest. SAveRUNNER predicts drug-disease associations by quantifying the interplay between the drug targets and the disease-associated proteins in the human interactome through the computation of a novel network-based similarity measure, which prioritizes associations between drugs and diseases located in the same network neighborhoods.
The algorithm was successfully applied to predict off-label drugs to be repositioned against the new human coronavirus (2019-nCoV/SARS-CoV-2), and it achieved a high accuracy in the identification of well-known drug indications, thus revealing itself as a powerful tool to rapidly detect potential novel medical indications for various drugs that are worth of further investigation. SAveRUNNER source code is freely available at https://github.com/giuliafiscon/SAveRUNNER.git , along with a comprehensive user guide.
目前,尚无针对新型冠状病毒病(COVID-19)的有效药物,尽管广泛开展了疫苗接种活动,但我们离群体免疫还很远。仍然容易受到病毒感染的人数太高,无法阻止新的疫情爆发,因此迫切需要寻找新的治疗选择来对抗 SARS-CoV-2 感染。药物重定位是一种从现有药物中寻找新用途的有效药物发现策略,与从头发现药物相比,它可以缩短时间并降低成本。
我们开发了一种基于网络的药物重定位工具,作为一个免费提供的 R 代码,称为 SAveRUNNER(搜索非标签药物和网络),旨在提供一个有前途的框架,以有效地检测目前市场上用于治疗感兴趣疾病的药物的新潜在适应症。SAveRUNNER 通过计算一种新的基于网络的相似性度量来量化药物靶标与人类相互作用组中疾病相关蛋白之间的相互作用,从而预测药物-疾病关联,该度量优先考虑位于同一网络邻域中的药物和疾病之间的关联。
该算法成功应用于预测新的人类冠状病毒(2019-nCoV/SARS-CoV-2)的非标签药物重新定位,并在识别已知药物适应症方面取得了很高的准确性,从而证明它是一种快速检测各种药物潜在新医疗适应症的强大工具,值得进一步研究。SAveRUNNER 的源代码可在 https://github.com/giuliafiscon/SAveRUNNER.git 上免费获得,同时还提供了详细的用户指南。