Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Department of Cardiology, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Biochem Biophys Res Commun. 2021 Oct 1;572:138-144. doi: 10.1016/j.bbrc.2021.07.076. Epub 2021 Aug 5.
Heart diseases are known as the most primary causes of mortality worldwide. Although many therapeutic approaches and medications are proposed for these diseases, the identification of novel therapeutics in fatal heart conditions is promptly demanded. Besides, the interplay between gene expression data and molecular docking provides several novel insights to discover more effective and specific drugs for the treatment of the diseases. This study aimed to discover potent therapeutic drugs in the heart diseases based on the expression profile of heart-specific genes exclusively. Initially, the heart-specific and highly expressed genes were identified by comparing the gene expression profile of different body tissues. Subsequently, the druggable-genes were identified using in silico techniques. The interaction between these druggable genes with more than 1600 FDA approved drugs was then investigated using the molecular docking simulation. By comprehensively analyzing RNA-sequencing data obtained from 949 normal tissue samples, 48 heart-specific genes were identified in both the heart development and function. Notably, of these, 24 heart-specific genes were capable to be considered as druggable genes, among which only MYBPC3, MYLK3, and SCN5A genes entered the molecular docking process due to their functions. Afterward, the pharmacokinetics properties of top 10 ligands with the highest binding affinity for these proteins were studied. Accordingly, methylergonovine, fosaprepitant, pralatrexate, daunorubicin, glecaprevir, digoxin, and venetoclax drugs were competent, in order to interact with the target proteins perfectly. It was shown that these medications can be used as specific drugs for the treatment of heart diseases after fulfilling further experiments in this regard.
心脏病是全球范围内导致死亡的最主要原因。尽管已经提出了许多治疗方法和药物来治疗这些疾病，但迫切需要在致命性心脏病况中发现新的治疗方法。此外，基因表达数据与分子对接的相互作用为发现更有效和更特异的治疗这些疾病的药物提供了一些新的见解。本研究旨在基于心脏特异性基因的表达谱，专门发现心脏病治疗中的有效药物。首先，通过比较不同身体组织的基因表达谱，确定了心脏特异性和高表达的基因。随后，使用计算机技术确定了可成药性基因。然后，使用分子对接模拟研究这些可成药性基因与 1600 多种 FDA 批准药物之间的相互作用。通过综合分析从 949 个正常组织样本中获得的 RNA-seq 数据，在心脏发育和功能中确定了 48 个心脏特异性基因。值得注意的是，在这些基因中，有 24 个心脏特异性基因可以被认为是可成药性基因，其中只有 MYBPC3、MYLK3 和 SCN5A 基因因其功能而进入分子对接过程。之后，研究了与这些蛋白质结合亲和力最高的前 10 个配体的药代动力学特性。因此，甲基麦角新碱、福沙匹坦、普拉曲沙、柔红霉素、glecaprevir、地高辛和 venetoclax 药物能够与靶蛋白完美相互作用。结果表明，这些药物在这方面进一步实验后，可作为治疗心脏病的特效药物。
