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Since the 2014 Ebola virus (EBOV) outbreak in West Africa there has been considerable effort towards developing drugs to treat Ebola virus disease and yet to date there is no FDA approved treatment. This is important as at the time of writing there is an ongoing outbreak in the Democratic Republic of the Congo. We have evaluated a small number of natural products, some of which had shown antiviral activity against other pathogens. This is exemplified with eugenol, which is found in high concentrations in multiple essential oils, and has shown antiviral activity against feline calicivirus, tomato yellow leaf curl virus, Influenza A virus, Herpes Simplex virus type 1 and 2, and four airborne phages. Four compounds possessed EC(50) values less than or equal to 11 μM. Of these, eugenol, had an EC(50) of 1.3 μM against EBOV and is present in several plants including clove, cinnamon, basil and bay. Eugenol is much smaller and structurally unlike any compound that has been previously identified as an inhibitor of EBOV, therefore it may provide new mechanistic insights. This compound is readily accessible in bulk quantities, is inexpensive, and has a long history of human consumption, which endorses the idea for further assessment as an antiviral therapeutic. This work also suggests that a more exhaustive assessment of natural product libraries against EBOV and other viruses is warranted to improve our ability to identify compounds that are so distinct from FDA approved drugs.

The recent outbreaks of the Ebola virus (EBOV) in Africa have brought global visibility to the shortage of available therapeutic options to treat patients infected with this or closely related viruses. We have recently computationally identified three molecules which have all demonstrated statistically significant efficacy in the mouse model of infection with mouse adapted Ebola virus (ma-EBOV). One of these molecules is the antimalarial pyronaridine tetraphosphate (IC(50) range of 0.82–1.30 μM against three strains of EBOV and IC(50) range of 1.01–2.72 μM against two strains of Marburg virus (MARV)) which is an approved drug in the European Union and used in combination with artesunate. To date, no small molecule drugs have shown statistically significant efficacy in the guinea pig model of EBOV infection. Pharmacokinetics and range-finding studies in guinea pigs directed us to a single 300mg/kg or 600mg/kg oral dose of pyronaridine 1hr after infection. Pyronaridine resulted in statistically significant survival of 40% at 300mg/kg and protected from a lethal challenge with EBOV. In comparison, oral favipiravir (300 mg/kg dosed once a day) had 43.5% survival. All animals in the vehicle treatment group succumbed to disease by study day 12 (100% mortality). The in vitro metabolism and metabolite identification of pyronaridine and another of our EBOV active molecules, tilorone, suggested significant species differences which may account for the efficacy or lack thereof, respectively in guinea pig. In summary, our studies with pyronaridine demonstrates its utility for repurposing as an antiviral against EBOV and MARV.

The task of international expert groups is to recommend the classification and naming of viruses. The ICTV Filoviridae Study Group and other experts have recently established an almost consistent classification and nomenclature for filoviruses. Here, further guidelines are suggested to include their natural genetic variants. First, this term is defined. Second, a template for full-length virus names (such as "Ebola virus H.sapiens-tc/COD/1995/Kikwit-9510621") is proposed. These names contain information on the identity of the virus (e.g., Ebola virus), isolation host (e.g., members of the species Homo sapiens), sampling location (e.g., Democratic Republic of the Congo (COD)), sampling year, genetic variant (e.g., Kikwit), and isolate (e.g., 9510621). Suffixes are proposed for individual names that clarify whether a given genetic variant has been characterized based on passage zero material (-wt), has been passaged in tissue/cell culture (-tc), is known from consensus sequence fragments only (-frag), or does (most likely) not exist anymore (-hist). We suggest that these comprehensive names are to be used specifically in the methods section of publications. Suitable abbreviations, also proposed here, could then be used throughout the text, while the full names could be used again in phylograms, tables, or figures if the contained information aids the interpretation of presented data. The proposed system is very similar to the well-known influenzavirus nomenclature and the nomenclature recently proposed for rotaviruses. If applied consistently, it would considerably simplify retrieval of sequence data from electronic databases and be a first important step toward a viral genome annotation standard as sought by the National Center for Biotechnology Information (NCBI). Furthermore, adoption of this nomenclature would increase the general understanding of filovirus-related publications and presentations and improve figures such as phylograms, alignments, and diagrams. Most importantly, it would counter the increasing ...