In silico drug repurposing for the treatment of heart diseases using gene expression data and molecular docking techniques

被引：7

作者：

Aalikhani, Mahdi ^{[1
]}

Alikhani, Mehrdad ^{[2
]}

Shamsabadi, Fatemeh ^{[1
,3
]}

Oladnabi, Morteza ^{[4
,5
,6
]}

Bazi, Zahra ^{[1
,5
]}

机构：

[1] Golestan Univ Med Sci, Sch Adv Technol Med, Dept Med Biotechnol, Gorgan, Golestan, Iran

[2] Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, Dept Cardiol, Tehran, Iran

[3] Golestan Univ Med Sci, Med Cellular & Mol Res Ctr, Gorgan, Golestan, Iran

[4] Golestan Univ Med Sci, Canc Res Ctr, Gorgan, Golestan, Iran

[5] Golestan Univ Med Sci, Stem Cell Res Ctr, Gorgan, Golestan, Iran

[6] Golestan Univ Med Sci, Ischem Disorders Res Ctr, Gorgan, Golestan, Iran

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2021年 / 572卷

关键词：

Drug discovery; Drug repurposing; Heart diseases; Molecular docking; RNA sequencing; DISCOVERY;

D O I：

10.1016/j.bbrc.2021.07.076

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (c) 2021 Elsevier Inc. All rights reserved.

引用

页码：138 / 144

页数：7

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