未经批准:SARS-CoV-2感染或COVID-19是一个重大的全球公共卫生问题,在药物开发方面需要紧急关注。跨膜蛋白酶丝氨酸2(TMPRSS2)是针对SARS-CoV-2的良好药物靶标,因为它在病毒进入细胞期间发挥了作用。植物化学物质作为TMPRSS2的潜在抑制剂的虚拟筛选可以导致发现用于治疗COVID-19的候选药物。
UNASSIGNED:该研究旨在从三种传统上用作抗病毒药物的药用植物中筛选132种植物化学物质;生姜(姜科),黄花蒿(菊科),和辣木.(辣根科),作为TMPRSS2的潜在抑制剂,以寻找治疗COVID-19的治疗选择。
UNASSIGNED:使用SWISS-MODEL的ProMod33.1.1程序建立了TMPRSS2的同源性模型。使用分子对接和分子动力学模拟检查化合物与TMPRSS2模型之间的结合亲和力和相互作用。药物相似性和ADMET(吸收,分布,新陈代谢,排泄,和毒性)的TMPRSS2的潜在抑制剂的性质也使用admetSAR网工具进行了评估。
未经批准:三种化合物,即,niazirin,槲皮素,与甲磺酸camostat(一种已知的TMPRSS2抑制剂)获得的-7.0kcal/mol相比,来自油茶菌的Moringyne表现出更好的分子相互作用,结合亲和力范围为-7.1至-8.0kcal/mol,作为一个控制。通过不违反5的Lipinski规则,所有三种化合物均表现出良好的药物样特性。根据分子动力学模拟,Niazirin和moringyne具有良好的ADMET性能,并且与TMPRSS2的相互作用稳定。然而,ADMET工具预测槲皮素潜在的肝毒性和诱变效应。
未经评估:这项研究证明了日氮素的潜力,槲皮素,和来自油菌的Moringyne,抑制人类TMPRSS2的活性,因此可能是进一步开发治疗或管理COVID-19的新药的良好候选者。
UNASSIGNED: SARS-CoV-2 infection or COVID-19 is a major global public health issue that requires urgent attention in terms of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19.
UNASSIGNED: The study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID-19.
UNASSIGNED: Homology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool.
UNASSIGNED: Three compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin.
UNASSIGNED: This study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19.