Computers in Biology and Medicine ( IF 7.7 ) Pub Date : 2021-07-23 , DOI: 10.1016/j.compbiomed.2021.104677 Akanksha Rajput 1 , Anamika Thakur 2 , Amber Rastogi 2 , Shubham Choudhury 1 , Manoj Kumar 2
Viral epidemics and pandemics are considered public health emergencies. However, traditional and novel antiviral discovery approaches are unable to mitigate them in a timely manner. Notably, drug repurposing emerged as an alternative strategy to provide antiviral solutions in a timely and cost-effective manner. In the literature, many FDA-approved drugs have been repurposed to inhibit viruses, while a few among them have also entered clinical trials. Using experimental data, we identified repurposed drugs against 14 viruses responsible for causing epidemics and pandemics such as SARS-CoV-2, SARS, Middle East respiratory syndrome, influenza H1N1, Ebola, Zika, Nipah, chikungunya, and others. We developed a novel computational “drug-target-drug” approach that uses the drug-targets extracted for specific drugs, which are experimentally validated in vitro or in vivo for antiviral activity. Furthermore, these extracted drug-targets were used to fetch the novel FDA-approved drugs for each virus and prioritize them by calculating their confidence scores. Pathway analysis showed that the majority of the extracted targets are involved in cancer and signaling pathways. For SARS-CoV-2, our method identified 21 potential repurposed drugs, of which 7 (e.g., baricitinib, ramipril, chlorpromazine, enalaprilat, etc.) have already entered clinical trials. The prioritized drug candidates were further validated using a molecular docking approach. Therefore, we anticipate success during the experimental validation of our predicted FDA-approved repurposed drugs against 14 viruses. This study will assist the scientific community in hastening research aimed at the development of antiviral therapeutics.
中文翻译:
通过药物目标网络分析计算识别针对引起流行病和大流行的病毒的再利用药物
病毒性流行病和大流行病被视为突发公共卫生事件。然而,传统和新颖的抗病毒发现方法无法及时缓解它们。值得注意的是,药物再利用成为一种及时且具有成本效益的方式提供抗病毒解决方案的替代策略。在文献中,许多 FDA 批准的药物已被重新用于抑制病毒,而其中一些也已进入临床试验。利用实验数据,我们确定了针对 14 种导致流行病和大流行病的病毒的再利用药物,例如 SARS-CoV-2、SARS、中东呼吸综合征、H1N1 流感、埃博拉病毒、寨卡病毒、尼帕病毒、基孔肯雅病毒等。我们开发了一种新的计算“药物-靶点-药物” 使用针对特定药物提取的药物靶点的方法,这些靶点在体外或体内经过实验验证用于抗病毒活性。此外,这些提取的药物靶标用于为每种病毒获取 FDA 批准的新型药物,并通过计算它们的置信度分数对它们进行优先排序。通路分析表明,大多数提取的靶标都与癌症和信号通路有关。对于 SARS-CoV-2,我们的方法确定了 21 种潜在的再利用药物,其中 7 种(例如,baricitinib、雷米普利、氯丙嗪、依那普利拉等)已经进入临床试验。使用分子对接方法进一步验证优先候选药物。因此,我们预计在我们预测的 FDA 批准的针对 14 种病毒的再利用药物的实验验证过程中会取得成功。这项研究将协助科学界加快旨在开发抗病毒疗法的研究。