Almeida-Pinto Francisca, Pinto Rui, Rocha João
Faculdade de Farmácia, Universidade de Lisboa, 1649-003, Lisbon, Portugal.
Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines (iMED.ULisboa), 1649-003, Lisbon, Portugal.
Infect Dis Ther. 2024 Jan;13(1):21-55. doi: 10.1007/s40121-023-00913-y. Epub 2024 Jan 19.
In 1976 Ebola revealed itself to the world, marking the beginning of a series of localized outbreaks. However, it was the Ebola outbreak that began in 2013 that incited fear and anxiety around the globe. Since then, our comprehension of the virus has been steadily expanding. Ebola virus (EBOV), belonging to the Orthoebolavirus genus of the Filoviridae family, possesses a non-segmented, negative single-stranded RNA genome comprising seven genes that encode multiple proteins. These proteins collectively orchestrate the intricate process of infecting host cells. It is not possible to view each protein as monofunctional. Instead, they synergistically contribute to the pathogenicity of the virus. Understanding this multifaceted replication cycle is crucial for the development of effective antiviral strategies. Currently, two antibody-based therapeutics have received approval for treating Ebola virus disease (EVD). In 2022, the first evidence-based clinical practice guideline dedicated to specific therapies for EVD was published. Although notable progress has been made in recent years, deaths still occur. Consequently, there is an urgent need to enhance the therapeutic options available to improve the outcomes of the disease. Emerging therapeutics can target viral proteins as direct-acting antivirals or host factors as host-directed antivirals. They both have advantages and disadvantages. One way to bypass some disadvantages is to repurpose already approved drugs for non-EVD indications to treat EVD. This review offers detailed insight into the role of each viral protein in the replication cycle of the virus, as understanding how the virus interacts with host cells is critical to understanding how emerging therapeutics exert their activity. Using this knowledge, this review delves into the intricate mechanisms of action of current and emerging therapeutics.
1976年,埃博拉病毒首次现身于世,标志着一系列局部疫情爆发的开端。然而,真正引发全球恐惧和焦虑的是始于2013年的埃博拉疫情。自那时起,我们对该病毒的认知在不断深入。埃博拉病毒(EBOV)属于丝状病毒科正埃博拉病毒属,拥有一个非节段性的负链单链RNA基因组,由七个基因组成,这些基因编码多种蛋白质。这些蛋白质共同协调病毒感染宿主细胞的复杂过程。不能将每种蛋白质视为单一功能的。相反,它们协同作用,共同影响病毒的致病性。了解这个多方面的复制周期对于开发有效的抗病毒策略至关重要。目前,两种基于抗体的疗法已获批准用于治疗埃博拉病毒病(EVD)。2022年,首个专门针对EVD特定疗法的循证临床实践指南发布。尽管近年来取得了显著进展,但仍有死亡病例发生。因此,迫切需要增加治疗选择以改善疾病的治疗效果。新兴疗法可以靶向病毒蛋白作为直接作用的抗病毒药物,或者靶向宿主因子作为宿主导向的抗病毒药物。它们都有优缺点。规避一些缺点的一种方法是将已批准用于非EVD适应症的药物重新用于治疗EVD。本综述详细阐述了每种病毒蛋白在病毒复制周期中的作用,因为了解病毒与宿主细胞的相互作用对于理解新兴疗法如何发挥作用至关重要。基于这些知识,本综述深入探讨了当前和新兴疗法的复杂作用机制。