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石墨烯与VP40的相互作用以及对埃博拉病毒基质细丝的潜在破坏

Graphene-VP40 interactions and potential disruption of the Ebola virus matrix filaments.

作者信息

Gc Jeevan B, Pokhrel Rudramani, Bhattarai Nisha, Johnson Kristen A, Gerstman Bernard S, Stahelin Robert V, Chapagain Prem P

机构信息

Department of Physics, Florida International University, Miami, FL 33199, United States.

Department of Chemistry and Biochemistry, The Eck Institute for Global Health, The Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, United States.

出版信息

Biochem Biophys Res Commun. 2017 Nov 4;493(1):176-181. doi: 10.1016/j.bbrc.2017.09.052. Epub 2017 Sep 13.

Abstract

Ebola virus infections cause hemorrhagic fever that often results in very high fatality rates. In addition to exploring vaccines, development of drugs is also essential for treating the disease and preventing the spread of the infection. The Ebola virus matrix protein VP40 exists in various conformational and oligomeric forms and is a potential pharmacological target for disrupting the virus life-cycle. Here we explored graphene-VP40 interactions using molecular dynamics simulations and graphene pelleting assays. We found that graphene sheets associate strongly with VP40 at various interfaces. We also found that the graphene is able to disrupt the C-terminal domain (CTD-CTD) interface of VP40 hexamers. This VP40 hexamer-hexamer interface is crucial in forming the Ebola viral matrix and disruption of this interface may provide a method to use graphene or similar nanoparticle based solutions as a disinfectant that can significantly reduce the spread of the disease and prevent an Ebola epidemic.

摘要

埃博拉病毒感染会引发出血热,常常导致极高的死亡率。除了研发疫苗,药物开发对于治疗该疾病以及防止感染传播也至关重要。埃博拉病毒基质蛋白VP40以多种构象和寡聚形式存在,是破坏病毒生命周期的一个潜在药理学靶点。在此,我们使用分子动力学模拟和石墨烯沉淀试验探究了石墨烯与VP40的相互作用。我们发现石墨烯片层在各种界面处都与VP40强烈结合。我们还发现石墨烯能够破坏VP40六聚体的C端结构域(CTD-CTD)界面。这种VP40六聚体-六聚体界面在形成埃博拉病毒基质过程中至关重要,而破坏该界面可能提供一种方法,利用基于石墨烯或类似纳米颗粒的溶液作为消毒剂,从而能够显著减少疾病传播并预防埃博拉疫情。

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