针对 COVID-19 合并症的可再利用药物组合的系统医学框架

S. Saranya, L. Thamanna, P. Chellapandi
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摘要

目前,疫苗已显示出对 SARS-CoV-2 新变种的疗效。本研究旨在开发一个系统医学框架,以预测和验证可重新用于治疗 COVID-19 及其合并症(特别是 2 型糖尿病和高血压)的药物组合。这项研究发现,肠道微生物可能会影响药物的作用、先天性免疫反应、肠道功能紊乱以及这些合并症患者对病毒的易感性。研究还发现,病毒的尖峰蛋白与 57 个人类基因相互作用,其中许多基因与食源性细菌有关。对疾病的富集分析表明,在感染 SARS-CoV-2 的患者中,关节炎和高血压是常见的合并症。包括氟伏沙明(Fluvoxamine)、多奈哌齐(Donepezil)和伊芬普地尔(Ifenprodil)在内的几种药物已被确定为可用于治疗高血压患者 COVID-19 的潜在再利用药物。此外,硝唑尼特和托珠单抗(抗病毒药)、杆菌肽(抗菌药)和格列齐特(抗糖尿病药)也被确定为潜在的可再利用药物。托西珠单抗和格列齐特是治疗 2 型糖尿病患者 COVID-19 的有效药物组合。还有人建议将托珠单抗和利多卡因联合使用,治疗感染食源性细菌的患者的 COVID-19。
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Systems medicine framework for repurposable drug combinations for COVID-19 comorbidities

Currently, vaccines have shown efficacy against new SARS-CoV-2 variants. This study aimed to develop a systems medicine framework that can predict and validate drug combinations that can be repurposed for treating COVID-19 and its comorbidities, specifically type 2 diabetes and hypertension. This study found that gut microbes could potentially influence the action of drugs, innate immune response, intestinal dysfunction, and susceptibility to the virus in individuals with these comorbidities. It was also discovered that the spike protein of the virus interacts with 57 human genes, many of which are linked to food-borne bacteria. An analysis of disease enrichment showed that arthritis and hypertension were frequently observed as comorbidities in patients infected with SARS-CoV-2. Several drugs, including Fluvoxamine, Donepezil, and Ifenprodil, have been identified as potentially repurposable drugs for treating COVID-19 in individuals with hypertension. Moreover, nitazoxanide and tocilizumab (antivirals), bacitracin (antibacterial), and gliclazide (antidiabetics) were also identified as potential repurposable drugs. Tocilizumab and gliclazide are effective drug combinations for treating COVID-19 in individuals with type 2 diabetes. A combination of tocilizumab and lidocaine has also been suggested for treating COVID-19 in individuals infected with food-borne bacteria.

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