Scientists have synthesised a broad spectrum antiviral molecule that may hold the key to protection against the hemorrhagic fever causing filoviruses. Not only that, but preliminary investigations suggest that it may also be effective against a wide range of other RNA viruses, a Nature study has reported.
Filoviruses, such as Ebola virus and Marburg virus, are members of a family of viruses called Filoviridae. These viruses are well known for their ability to cause severe hemorrhagic fevers in humans and their high case fatality rates, which sometimes exceeds 90%. Transmission occurs via contact with infected body fluids such as blood. Like many other viruses initial infection usually presents with flu-like symptoms, but as disease progresses organs such as the liver and kidneys begin to stop functioning and severe hemorrhage often occurs.
Unfortunately there are no licensed drugs or vaccines for filoviruses and those that are currently in the developmental stage are highly virus specific and therefore limited in their use. This has presented the need for a therapeutic agent which can tackle multiple different filoviruses in outbreak prone areas, which is exactly what scientists have been working on in this study.
A molecule called BCX4430 was designed to inhibit a part of the virus, RNA polymerase, which makes new copies of the viral genome which is composed of RNA. This molecule is structurally similar to something found in our bodies called adenosine, and the virus is tricked into incorporating this fatal mimic into its growing RNA strands, preventing further RNA synthesis and therefore viral replication.
The team didn’t only test this new molecule on filoviruses in vitro; they also investigated numerous other RNA viruses such as measles virus, dengue virus, Yellow Fever virus and SARS virus. They found BCX4430 exerted specific antiviral effects against these viruses also, demonstrating its broad spectrum activity.
In order to further investigate the efficacy of the compound and to probe for potential toxic effects which could limit its use in a clinical setting, the researchers tested how BXC4430 fared in animal models. After proving that the compound could protect mice against lethal doses of Ebola virus, the researchers turned to non-human primate models. Cynomolgus macaques were infected with a lethal dose of Marburg virus and were given daily doses of BXC4430 from between 1-48 hours post-infection.
All of the control animals succumbed to disease and died by day 12, whereas all of the animals starting BXC4430 treatment between 24 and 48 hours post-infection survived. Only one monkey in the treatment group died, which was treated with BXC4430 beginning one hour after infection. Furthermore, the surviving monkeys did not present hemorrhagic disease and the molecule was found to be well tolerated with no signs of systemic toxicity.
Although it’s too early to tell how this may fare in humans, additional studies are currently underway which will hopefully lead to the compound being moved forward into human phase 1 clinical trials.
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