University of Science and Technology, Zewail City, Giza, 12578, Egypt.
Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Sci Rep. 2022 Jul 13;12(1):11934. doi: 10.1038/s41598-022-15898-w.
COVID-19 is a global pandemic impacting the daily living of millions. As variants of the virus evolve, a complete comprehension of the disease and drug targets becomes a decisive duty. The Omicron variant, for example, has a notably high transmission rate verified in 155 countries. We performed integrative transcriptomic and network analyses to identify drug targets and diagnostic biomarkers and repurpose FDA-approved drugs for SARS-CoV-2. Upon the enrichment of 464 differentially expressed genes, pathways regulating the host cell cycle were significant. Regulatory and interaction networks featured hsa-mir-93-5p and hsa-mir-17-5p as blood biomarkers while hsa-mir-15b-5p as an antiviral agent. MYB, RRM2, ERG, CENPF, CIT, and TOP2A are potential drug targets for treatment. HMOX1 is suggested as a prognostic biomarker. Enhancing HMOX1 expression by neem plant extract might be a therapeutic alternative. We constructed a drug-gene network for FDA-approved drugs to be repurposed against the infection. The key drugs retrieved were members of anthracyclines, mitotic inhibitors, anti-tumor antibiotics, and CDK1 inhibitors. Additionally, hydroxyquinone and digitoxin are potent TOP2A inhibitors. Hydroxyurea, cytarabine, gemcitabine, sotalol, and amiodarone can also be redirected against COVID-19. The analysis enforced the repositioning of fluorouracil and doxorubicin, especially that they have multiple drug targets, hence less probability of resistance.
COVID-19 是一种全球性大流行病，影响着数百万人的日常生活。随着病毒变体的不断进化，对该疾病和药物靶点的全面理解成为一项决定性的任务。例如，奥密克戎变体在 155 个国家的传播率非常高。我们进行了整合转录组和网络分析，以确定药物靶点和诊断生物标志物，并重新利用 FDA 批准的药物来治疗 SARS-CoV-2。在富集了 464 个差异表达基因后，调控宿主细胞周期的途径变得非常显著。调控和相互作用网络以 hsa-mir-93-5p 和 hsa-mir-17-5p 作为血液生物标志物，而 hsa-mir-15b-5p 作为抗病毒药物。MYB、RRM2、ERG、CENPF、CIT 和 TOP2A 是治疗的潜在药物靶点。HMOX1 被建议作为预后生物标志物。用楝树植物提取物增强 HMOX1 的表达可能是一种治疗替代方法。我们构建了一个针对 FDA 批准药物的药物-基因网络，以重新用于对抗感染。检索到的关键药物是蒽环类药物、有丝分裂抑制剂、抗肿瘤抗生素和 CDK1 抑制剂的成员。此外，羟基喹啉和洋地黄毒苷是有效的 TOP2A 抑制剂。羟基脲、阿糖胞苷、吉西他滨、索他洛尔和胺碘酮也可以针对 COVID-19 进行重新定位。该分析加强了氟尿嘧啶和阿霉素的重新定位，特别是它们具有多个药物靶点，因此耐药的可能性较小。
