Scientists have found that an oral antiviral drug successfully prevents monkeys from dying after an Ebola infection, an advance that may prevent future outbreaks of the deadly virus.
The deadly Ebola virus is highly lethal to humans and nonhuman primates (NHPs) with death rates close to 90 per cent of infected individuals.
For instance, the 2013–2016 West African Ebola virus disease (EVD) epidemic caused 11,325 deaths among 28,600 infected people while another outbreak between 2018 and 2020 in Democratic Republic of Congo (DRC) and Uganda killed 2299 individuals out of 3481 infection cases.
While antibody-based treatments have shown some success in animal and human trials, the combination of cold-chain transport and storage requirements pose substantial challenges to contain outbreaks, researchers say.
Thus, there is a need for developing oral pills that can be rapidly and widely deployed to save lives and contain the spread of the virus in resource-limited regions.
“Oral antivirals have several advantages over parenterally administered drugs, including potential to be easier to supply, store, distribute, and administer,” scientists explained.
The drug Obeldesivir (ODV) was previously found to have broad activity across several RNA viruses – including the filovirus family to which Ebola belongs – when given 24 hours after exposure.
However, in the previous research, scientists used intramuscular delivery of the virus into macaques, which causes a much faster disease course that makes it harder to track the drug’s effect.
In the latest study, published in the journal Science Advances, researchers found that ODV protects 100 per cent of rhesus macaques exposed to the highly potent Makona variant of Ebola virus via mucosal administration.
Five rhesus and five crab-eating macaques received daily ODV for 10 days starting 24 hours post-exposure, while three monkeys served as controls.
Scientists found that ODV provided 100 per cent protection against death for rhesus macaques and 80 per cent protection for the crab-eating monkeys.
Since the disease progressed slower under the latest virus administration route, researchers could also explore ODV’s mechanisms of action.
They found that the treated monkeys had higher expression of proteins that support activation of the immune system’s T cells.
Monkeys provided ODV also appeared to have better anti-inflammatory action and dampening of any severe immune reaction.
Overall, researchers say the results support the potential of ODV as an oral postexposure prophylaxis.
“These findings suggest that ODV treatment affords the opportunity for the development of adaptive immunity while mitigating excessive inflammation, potentially preventing fatal outcomes,” they wrote.
Scientists hope to further understand how a delayed ODV treatment would affect immune responses.
“However, even if ODV is only effective when given between 24 hours after EBOV exposure and before the onset of illness, it may have utility in combating EBOV outbreaks and for subjects with known exposures to EBOV, including accidents in the clinic or laboratories,” they wrote.
