Abstract
The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.
Highlights
Ebola virus (EBOV) and Marburg virus (MARV) belong to the Filoviridae family and are enveloped, single-stranded, negative-sense RNA viruses with filamentous morphology
We evaluated several hundred extracts of Traditional Chinese medicines (TCMs) in an effort to identify potential antiviral agents against filoviruses and other emerging viral pathogens, and showed that extracts of the plant Rhodiola rosea L. can inhibit the entry and infection of Ebola and Marburg viruses
We have identified that two chemically related compounds, gallic acid and ellagic acid isolated from R. rosea and commercially available, can effectively block entry of Ebola virus, and to a lesser extent, Marburg virus
Summary
Ebola virus (EBOV) and Marburg virus (MARV) belong to the Filoviridae family and are enveloped, single-stranded, negative-sense RNA viruses with filamentous morphology. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with mortality rates up to 90% [1]. Natural products are considered to be a natural combinatorial chemical source because they contain structurally diversified bioactive chemicals, making them a valuable reservoir for new drug discovery. Natural products or their direct derivatives account for 34% of new medicines approved by the US Food and Drug Administration (FDA) between 1981 and 2010 [3].
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