Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus in which human infection became relevant during recent outbreaks in Latin America due to its unrecognized association with fetal neurological disorders. Currently, there are no approved effective antivirals or vaccines for the treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV reference strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the latter. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine the potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across flavivirus, susceptible to be blocked by modified more specific adamantane compounds.
Highlights
We observed a dose-dependent reducreduction in Zika virus (ZIKV) titers upon incubation with both amantadine and rimantadine hytion in ZIKV titers upon incubation with both amantadine and rimantadine hydrochlodrochlorides at all tested times post-infection, as depicted in the raw data and in plots rides at all tested times post-infection, as depicted in the raw data and in plots shown in shown in Figures 1 and 2, respectively
No specific antiviral therapies have been approved for the treatment of ZIKV infections
The search for drugs against ZIKV is being conducted through different approaches, such as the screening of existing compound libraries and the repurposing of validated drugs used in the clinic for the treatment of other diseases, including many already known and used antivirals [34]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Zika virus (ZIKV) is a member of the genus Flavivirus within the Flaviviridae family, first isolated in 1947 from a rhesus macaque in the Zika Forest, Uganda [1]. It is a mosquitoborne arbovirus transmitted to humans by Aedes aegypti and Aedes albopictus [2]. The virion comprises an enveloped spherical particle with a positive single-stranded RNA genome, phylogenetically related to other flaviviruses of medical importance such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) [3]
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