Ahmed Faheem, Ho Son Gi, Samantasinghar Anupama, Memon Fida Hussain, Rahim Chethikkattuveli Salih Abdul, Soomro Afaque Manzoor, Sunildutt Naina, Kim Kyung Hwan, Choi Kyung Hyun
Department of Mechatronics Engineering, Jeju National University, Republic of Korea.
BioSpero, Inc., Jeju, Republic of Korea.
Comput Struct Biotechnol J. 2022 Nov 9;20:6097-6107. doi: 10.1016/j.csbj.2022.10.046. eCollection 2022.
Psoriasis is a skin disease which results in scales on the skin caused by flaky patches. Psoriasis is triggered by various conditions such as drug reactions, trauma, and skin infection etc. Globally, there are 125 million people affected by psoriasis and yet there is no effective treatment available, and it emphasizes the need for discovery of efficacious treatments. De-novo drug development takes 10-17 years and $2-$3 billion of investment with <10 % success rate to bring drug from concept to a market ready product. A possible alternative is drug repurposing, which aims at finding other indications of already approved drugs. In this study, a computational drug repurposing framework is developed and applied to differential gene expressions of Psoriasis targets obtained from the publicly available database (GEO). This strategy uses the gene expression signatures of the Psoriasis and compares it with perturbagen available in the CMap. Based on the connected signature drugs are ranked which could possibly reverse the signatures to stop the psoriasis. The drugs with most negative connectivity scores are ranked efficient and vice versa. The top hit drugs are verified using the literature survey of the peer reviewed journal, electronic health records, patents, and hospital database. As a result, 50/150 and 37/150 drugs are confirmed to have anti-psoriasis efficacy in two datasets. Top 10 drugs are suggested as potential repurposable drugs for psoriasis. This study offers, a powerful yet simple approach for rapid identification of potential drug repurposing candidates in Psoriasis and any disease of interest.
银屑病是一种皮肤病，会导致皮肤出现由片状斑块引起的鳞屑。银屑病由多种情况引发，如药物反应、外伤和皮肤感染等。在全球范围内，有1.25亿人受银屑病影响，但目前尚无有效的治疗方法，这凸显了发现有效治疗方法的必要性。从头研发药物需要10至17年，投资20亿至30亿美元，将药物从概念转化为可上市产品的成功率低于10%。一种可能的替代方法是药物重新利用，其目的是寻找已批准药物的其他适应症。在本研究中，开发了一种计算药物重新利用框架，并将其应用于从公开数据库（GEO）获得的银屑病靶点的差异基因表达。该策略利用银屑病的基因表达特征，并将其与CMap中可用的干扰剂进行比较。基于连接性对可能逆转特征以阻止银屑病的药物进行排名。连接性得分最负的药物被评为有效，反之亦然。通过对同行评审期刊、电子健康记录、专利和医院数据库的文献调查来验证排名靠前的药物。结果，在两个数据集中分别有50/150和37/150种药物被证实具有抗银屑病功效。前10种药物被建议作为银屑病潜在的可重新利用药物。这项研究为快速识别银屑病及任何感兴趣疾病中潜在的药物重新利用候选药物提供了一种强大而简单的方法。
