Spread via the bite of infected daytime-active Aedes mosquitoes (or by sexual transmission), the flavivirus Zika was responsible for an epidemic in the Americas in 2015-2017. The World Health Organization (WHO) estimated that Zika affected over 800,000 people throughout the continent within those two years, whilst other sources reveal that the number of cases surpassed the 1.5 million mark within Brazil alone! The infection known as Zika fever, or Zika virus (ZIKV) disease, causes minor symptoms like a very mild form of dengue fever. Infrequently it progresses into Guillain–Barré syndrome, however, the impact that Zika infection can have on fetal development in pregnant women is most worrisome. Infection during pregnancy can result in microcephaly, severe brain malformations, and other birth defects. Since 2015, there have been over 3,700 confirmed cases of congenital syndromes associated to ZIKV, just within the Americas (WHO).
Without an approved antiviral agent to prevent, treat or cure infections, more studies are called for to better understand the pathogenesis of ZIVK and to help develop specific medical countermeasures. Within this blog series we will summarize the findings of pertinent studies that focus on the prevention of, or treatments for Zika infection.
Recently, a group of researchers in the US investigated Emetine, an FDA-approved drug for amoebiasis that was identified in their ZIKV drug repositioning screen. Nature Article: Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry.
Kirill Gorshkov, PhD Biologist, commented that their goal is to motivate more research into the use of this drug with pregnant women. If we can prevent the development of microcephaly, either by stopping the infection in the mother, or preventing the infection in the mother from infecting the child, the world will be better off.
The antiviral properties of Emetine had been previously demonstrated but its inhibitory effects and the mechanism of action in ZIKV were unknown. Interestingly, this study uncovered that Emetine bridges what normally constitutes two independent antiviral development paths by targeting the viral polymerase directly and host cellular proteins, the latter of which makes it difficult for the virus to develop resistance to a drug. The caveat is, Emetine’s not generally recommended for use during pregnancy due to potentially toxic effects to the fetus.
That said, because of its potential for treating the severe ZIKV infections that cause significant neurological disorders in new-born’s and the fact Emetine’s use in pregnancy has been recorded, they surmise that this same precedent should be considered for Emetine as for Zidovudine (AZT). AZT was approved in the late 1980’s in the battle against HIV infected adults, then subsequently for pregnant women in 1994 post fetal toxicity testing.
The authors also surmised that the drug design strategy of targeting multiple viral and host cell targets could be a new approach for the next generation of antiviral agents.
We would like to congratulate the team on this important contribution to science.
Stay tuned for the next blog in the series where we’ll look at the crystal structure of ZIKV C protein to determine the full scope of functions possessed by this component.