Budak Cafer, Mençik Vasfiye, Gider Veysel
Department of Biomedical Engineering, Dicle University, Diyarbakır, Turkey.
Department of Electric-Electronic Engineering, Dicle University, Diyarbakır, Turkey.
J Biomol Struct Dyn. 2023 Feb;41(2):659-671. doi: 10.1080/07391102.2021.2010601. Epub 2021 Dec 8.
COVID-19 is a worldwide health crisis seriously endangering the arsenal of antiviral and antibiotic drugs. It is urgent to find an effective antiviral drug against pandemic caused by the severe acute respiratory syndrome (Sars-Cov-2), which increases global health concerns. As it can be expensive and time-consuming to develop specific antiviral drugs, reuse of FDA-approved drugs that provide an opportunity to rapidly distribute effective therapeutics can allow to provide treatments with known preclinical, pharmacokinetic, pharmacodynamic and toxicity profiles that can quickly enter in clinical trials. In this study, using the structural information of molecules and proteins, a list of repurposed drug candidates was prepared again with the graph neural network-based GEFA model. The data set from the public databases DrugBank and PubChem were used for analysis. Using the Tanimoto/jaccard similarity analysis, a list of similar drugs was prepared by comparing the drugs used in the treatment of COVID-19 with the drugs used in the treatment of other diseases. The resultant drugs were compared with the drugs used in lung cancer and repurposed drugs were obtained again by calculating the binding strength between a drug and a target. The kinase inhibitors (erlotinib, lapatinib, vandetanib, pazopanib, cediranib, dasatinib, linifanib and tozasertib) obtained from the study can be used as an alternative for the treatment of COVID-19, as a combination of blocking agents (gefitinib, osimertinib, fedratinib, baricitinib, imatinib, sunitinib and ponatinib) such as ABL2, ABL1, EGFR, AAK1, FLT3 and JAK1, or antiviral therapies (ribavirin, ritonavir-lopinavir and remdesivir).Communicated by Ramaswamy H. Sarma.
新冠病毒病(COVID-19)是一场全球健康危机,严重危及抗病毒和抗生素药物的储备。迫切需要找到一种有效的抗病毒药物来对抗由严重急性呼吸综合征冠状病毒2(Sars-CoV-2)引起的大流行,这增加了全球对健康问题的担忧。由于开发特定的抗病毒药物可能既昂贵又耗时,重新利用已获美国食品药品监督管理局(FDA)批准的药物,这些药物有机会迅速分发有效的治疗药物,能够提供具有已知临床前、药代动力学、药效学和毒性特征的治疗方法,从而可以迅速进入临床试验。在本研究中,利用分子和蛋白质的结构信息,再次使用基于图神经网络的GEFA模型制备了一系列重新利用的候选药物。来自公共数据库DrugBank和PubChem的数据集用于分析。使用Tanimoto/杰卡德相似性分析,通过将用于治疗COVID-19的药物与用于治疗其他疾病的药物进行比较,制备了一份相似药物清单。将所得药物与用于治疗肺癌的药物进行比较,并通过计算药物与靶点之间的结合强度再次获得重新利用的药物。从该研究中获得的激酶抑制剂(厄洛替尼、拉帕替尼、凡德他尼、帕唑帕尼、西地尼布、达沙替尼、利尼伐尼和托扎司他)可用作治疗COVID-19的替代药物,作为ABL2、ABL1、表皮生长因子受体(EGFR)、AAK1、FMS样酪氨酸激酶3(FLT3)和Janus激酶1(JAK1)等阻断剂(吉非替尼、奥希替尼、非格司亭、巴瑞替尼、伊马替尼、舒尼替尼和波纳替尼)的组合,或抗病毒疗法(利巴韦林、洛匹那韦利托那韦和瑞德西韦)。由拉马斯瓦米·H·萨尔马传达。