纳米药物传递系统中乳铁蛋白组合的药物再利用以对抗严重急性呼吸综合征冠状病毒-2感染

A. Barakat, A. Al-Majid, Gehad Lotfy, Mohamed Ali, Ahmed Mostafa, Y. Elshaier
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引用次数: 8

摘要

本文报道了一种利用化学信息学和化学转化方法对美国食品和药物管理局(FDA)批准的药物和临床前实体进行药物再利用的方法,目的是发现更安全的新型有效的COVID-19选择性抑制剂。我们检测了乳铁蛋白对严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)的作用。乳铁蛋白不仅可以作为治疗药物,还可以作为纳米载体。在被批准用于帮助控制COVID-19大流行的不同重新用途药物中,我们重点研究了纳米药物递送形式的硝唑尼特。与硝唑昔尼特联合使用后,乳铁蛋白活性提高[半最大抑制浓度(IC 50) = 2.72, 1.34,选择性指数(SI)分别为25和32]。这些结果将有助于我们提高乳铁蛋白作为各种选定药物的纳米载体的活性。此外,螺菌吲哚支架对SARS-CoV-2和中东呼吸综合征(MERS)-CoV的抗病毒活性显示出有趣的结果,ic50分别为0.03和0.001 mM。分子模拟研究表明,硝唑尼特与阿比多尔具有高度的相似性。对接输出强调了苯胺在药物活性中的重要性,因为它能够形成必需的HB主蛋白酶和刺突蛋白活性位点。通过了解结合模式,这些数据将有助于我们设计新的抗SARS-CoV-2生物活性候选药物。
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Drug Repurposing of Lactoferrin Combination in a Nanodrug Delivery System to Combat Severe Acute Respiratory Syndrome Coronavirus-2 Infection
A drug repurposing approach for Food and Drug Administration (FDA)-approved drugs and preclinical entity by using cheminformatics and chemical transformational method, with the objective of discovering safer novel potent inhibitors that are selective for COVID-19, is reported. We examined the action of lactoferrin against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Lactoferrin was tested not only as therapy but also as a nanocarrier. Among the different repurposed drugs approved to help control the COVID-19 pandemic, we focused on nitazoxanide in a nanodrug delivery form. Lactoferrin activity improved after it was used in combination with nitazoxanide [half-maximal inhibitory concentration (IC 50 ) = 2.72, 1.34 with Selectivity Index (SI) = 25 and 32, respectively]. These results will help us enhance the activity of lactoferrin as a nanocarrier for a variety of selected drugs. In addition, the antiviral activity of the spirooxindole scaffold showed interesting results against SARS-CoV-2 as well as Middle East respiratory syndrome (MERS)-CoV with an IC 50 of 0.03 and 0.001 mM, respectively. The molecular modeling study revealed that nitazoxanide has a high similarity to arbidol. Docking outputs emphasize the importance of anilide functionality in drug activity because of its ability to form essential HB main protease and spike protein active sites. By understanding the binding mode, these data will help us design new bioactive drug candidates against SARS-CoV-2.
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49 weeks
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