The filoviruses Ebola and Marburg are zoonotic agents that are classified as both biosafety level 4 and category A list pathogens. These viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in Central Africa. Their natural reservoir has not been definitely identified, but certain species of African bat have been associated with Ebola and Marburg infections. Currently, there are no licensed options available for either treatment or prophylaxis. Different animal models have been developed for filoviruses including mouse, guinea pig and nonhuman primates. The 'gold standard' animal models for pathogenesis, treatment and vaccine studies are rhesus and cynomolgus macaques. This article provides a brief overview of the clinical picture and the pathology/pathogenesis of human filovirus infections. The current animal model options are discussed and compared with regard to their value in different applications. In general, the small animal models, in particular the mouse, are the most feasible for high biocontainment facilities and they offer the most options for research owing to the greater availability of immunologic and genetic tools. However, their mimicry of the human diseases as well as their predictive value for therapeutic efficacy in primates is limited, thereby making them, at best, valuable initial screening tools for pathophysiology, treatment and vaccine studies.
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http://dx.doi.org/10.1242/dmm.000471 | DOI Listing |
J Clin Epidemiol
December 2024
Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Objective: To describe the processes of reconciling overlapping guidance and prioritizing practice questions for a World Health Organization (WHO) guideline on Infection Prevention and Control (IPC) for Ebola and Marburg disease.
Methods: This work involved the reconciliation of guidance, the generation of potential practice questions and the prioritization of those questions. Contributors included the WHO secretariat, the WHO steering group, the guideline methodologists, and the guideline development group (GDG).
Emerg Microbes Infect
December 2024
Institute of Virology, Philipps-Universität Marburg, 35043 Marburg, Germany.
Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral transcription activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in the regulation of this process by recruiting both the regulatory subunit B56 of PP2A and its substrate VP30 to initiate VP30 dephosphorylation and hence viral transcription. Both binding sites are located in close proximity to each other in NP's C-terminal disordered region.
View Article and Find Full Text PDFNPJ Vaccines
December 2024
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.
View Article and Find Full Text PDFInt J Infect Dis
December 2024
Department of General Medicine and Surgery, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda. Electronic address:
Marburg virus disease (MVD) is a highly virulent and often fatal disease caused by the Marburg virus, a member of the Filoviridae family, closely related to the Ebola virus. Historically, outbreaks have been sporadic but lethal across various African countries, with high case fatality rates (CFRs). In 2023, significant outbreaks occurred in Tanzania and Equatorial Guinea, with CFRs of 62.
View Article and Find Full Text PDFJ Med Chem
December 2024
UICentre: Drug Discovery, University of Illinois Chicago, Chicago, Illinois 60612, United States.
Ebola and Marburg (EBOV and MARV) filoviral infections lead to fatal hemorrhagic fevers and have caused over 30 outbreaks in the last 50 years. Currently, there are no FDA-approved small molecule therapeutics for effectively treating filoviral diseases. To address this unmet medical need, we have conducted a systematic structural optimization of an early lead compound, -(4-(4-methylpiperidin-1-yl)-3-(trifluoromethyl)phenyl)-4-(morpholinomethyl)benzamide (), borne from our previously reported hit-to-lead effort.
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