期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 607, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.121023
关键词
COVID-19; SARS-COV-2 main protease; Drug repurposing; SSRIs; Molecular docking; Fluoxetine hydrochloride; Lipid polymer hybrid
This study utilized molecular docking and nano-hybrid technology to validate the therapeutic potential of SSRIs against COVID-19, particularly the binding of Fluoxetine hydrochloride (FH) with the SARS-COV-2 main protease. Optimization of the FH-LPH nanoparticle formulation improved loading efficiency and efficacy.
Up to date, there were no approved drugs against coronavirus (COVID-19) disease that dangerously affects global health and the economy. Repurposing the existing drugs would be a promising approach for COVID-19 management. The antidepressant drugs, selective serotonin reuptake inhibitors (SSRIs) class, have antiviral, antiinflammatory, and anticoagulant effects, which makes them auspicious drugs for COVID 19 treatment. Therefore, this study aimed to predict the possible therapeutic activity of SSRIs against COVID-19. Firstly, molecular docking studies were performed to hypothesize the possible interaction of SSRIs to the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-COV-2) main protease. Secondly, the candidate drug was loaded in lipid polymer hybrid (LPH) nanoparticles to enhance its activity. The studied SSRIs were Fluoxetine hydrochloride (FH), Atomoxteine, Paroxetine, Nisoxteine, Repoxteine RR, and Repoxteine SS. Interestingly, FH could effectively bind with SARS-COV-2 main protease via hydrogen bond formation with low binding energy (-6.7 kcal/mol). Moreover, the optimization of FH-LPH formulation achieved 65.1 +/- 2.7% encapsulation efficiency, 10.3 +/- 0.4% loading efficiency, 98.5 +/- 3.5 nm particle size, and -10.5 +/- 0.45 mV zeta potential. Additionally, it improved cellular internalization in a time-dependent manner with good biocompatibility on Human lung fibroblast (CCD-19Lu) cells. Therefore, the study suggested the potential activity of FH-LPH nanoparticles against the COVID-19 pandemic.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据