Wang Xin, Wang Han, Yin Guosheng, Zhang Yan Dora
Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong SAR, China.
Department of Mathematics, Imperial College London, London, The United Kingdom.
Heliyon. 2023 Mar;9(3):e14059. doi: 10.1016/j.heliyon.2023.e14059. Epub 2023 Feb 24.
In the severe acute respiratory coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to develop effective treatments. Through a network-based drug repurposing approach, several effective drug candidates are identified for treating COVID-19 patients in different clinical stages. The proposed approach takes advantage of computational prediction methods by integrating publicly available clinical transcriptome and experimental data. We identify 51 drugs that regulate proteins interacted with SARS-CoV-2 protein through biological pathways against COVID-19, some of which have been experimented in clinical trials. Among the repurposed drug candidates, lovastatin leads to differential gene expression in clinical transcriptome for mild COVID-19 patients, and estradiol cypionate mainly regulates hormone-related biological functions to treat severe COVID-19 patients. Multi-target mechanisms of drug candidates are also explored. Erlotinib targets the viral protein interacted with cytokine and cytokine receptors to affect SARS-CoV-2 attachment and invasion. Lovastatin and testosterone block the angiotensin system to suppress the SARS-CoV-2 infection. In summary, our study has identified effective drug candidates against COVID-19 for patients in different clinical stages and provides comprehensive understanding of potential drug mechanisms.
在2019年冠状病毒病（COVID-19）大流行的严重急性呼吸综合征中，迫切需要开发有效的治疗方法。通过基于网络的药物重新利用方法，确定了几种有效的候选药物，用于治疗不同临床阶段的COVID-19患者。所提出的方法通过整合公开可用的临床转录组和实验数据，利用计算预测方法。我们确定了51种通过针对COVID-19的生物途径调节与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）蛋白相互作用的蛋白质的药物，其中一些已在临床试验中进行了实验。在重新利用的候选药物中，洛伐他汀导致轻度COVID-19患者临床转录组中的基因表达差异，而环丙孕酮主要调节激素相关的生物学功能以治疗重度COVID-19患者。还探索了候选药物的多靶点机制。厄洛替尼靶向与细胞因子和细胞因子受体相互作用的病毒蛋白，以影响SARS-CoV-2的附着和入侵。洛伐他汀和睾酮阻断血管紧张素系统以抑制SARS-CoV-2感染。总之，我们的研究确定了针对不同临床阶段COVID-19患者的有效候选药物，并提供了对潜在药物机制的全面理解。
