Identifying Novel Ebola Therapeutics

The Ebola virus (EBOV), the causative agent of Ebola virus disease (EVD), is a severe and often fatal illness. Zoonotic in origin, the disease is transmitted from wild animals to humans, with numerous species acting as a disease reservoir. Certain bat species are thought to be the primary source, and they subsequently pass the disease to other species, such as humans, apes, monkeys, and antelopes. Importantly, the disease is also capable of human-to-human transmission. Frequent outbreaks occur in sub-Saharan Africa, but the disease has threatened to spread to other continents, with a few notable cases occurring in the USA in 2014 causing widespread panic. One of the major challenges of controlled Ebola is the speed at which symptoms can manifest. The resulting hemorrhagic fever features an unpleasant medley of symptoms including vomiting, diarrhea, rash, symptoms of impaired kidney and liver function, and in some cases internal and external bleeding, such as oozing from the gums or bloody excrement (1). All of which results in a case fatality rate of around 50%, although these have varied from 25% to 90% in past outbreaks.

Vaccines do exist for the disease, but unfortunately there are limited therapeutic options once the disease is caught, with an urgent need to develop novel anti-EBOV agents. Over 50% of approved drugs are natural products or their derivatives and mimics, highlighting the importance of plants as a source for drug discovery (2).

As such, researchers actively searched for inhibitors of the Ebola virus from over 500 medicinal plant extracts, utilizing size‑exclusion chromatography (SEC) and high performance liquid chromatography (HPLC) alongside cell-based assays with replication-incompetent pseudotyped viral particles to identify antiviral lead compounds (3), in a so-called “one‑stone‑two‑birds” protocol first reported in 2011 (4). This led to the discovery of Maesa perlarius as an anti-EBOV plant lead. Extracts from the stems of this plant showed an inhibitory effect against Ebola-virus-pseudotyped particles (EBOVpp). Further investigation identified these as flavan-3-ol oligomers, and in particular B-type procyanidins belonging to a class of condensed tannins. Researchers believe these molecules can be used as scaffolds for a target-oriented synthesis of additional analogues possessing improved anti-EBOV potency.

References

1. https://www.who.int/health-topics/ebola (Accessed: 16/03/2022).
2. D.J. Newman and G.M. Cragg, J. Nat. Prod. 83, 770–803 (2020).
3. N.Y. Tsang et al., Int. J. Mol. Sci. 23, 2620 (2022). doi: https://doi.org/ 10.3390/ijms23052620
4. E. Rumschlag-Booms et al., J. Antivir. Antiretrovir. 3, 8–10 (2011).