Abstract
The recent outbreak of infection with Zika virus (ZIKV; Flaviviridae) has attracted attention to this previously neglected mosquito-borne pathogen and the need for efficient therapies. Since flavivirus replication is generally known to be dependent on fatty acid biosynthesis, two inhibitors of this pathway, 5-(tetradecyloxyl)-2-furoic acid (TOFA) and cerulenin, were tested for their potentiality to inhibit virus replication. At concentrations previously shown to inhibit the replication of other flaviviruses, neither drug had a significant antiviral affect against ZIKV, but reduced the replication of the non-related mosquito-borne Semliki Forest virus (Togaviridae).
Highlights
Arboviruses are a diverse group of viruses that are transmitted by arthropod vectors, including mosquitoes, ticks and midges and belong to four main viral families (Togaviridae, Flaviviridae, Bunyaviridae and Reoviridae)
Fatty acid synthesis in the cytoplasm of eukaryotic cells requires three different enzymes that act in an orchestrated manner: ATP citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN)
The results of TOFA treatment on Zika virus (ZIKV) showed that, if Nluc levels were measured 12 hpi (Fig. 1D, MOI 1, drugs added at 4 hpi) at the highest drug concentration, only a 20% reduction in Nluc levels was observed, indicating a weak decrease in ZIKV replication
Summary
Arboviruses are a diverse group of viruses that are transmitted by arthropod vectors, including mosquitoes, ticks and midges and belong to four main viral families (Togaviridae, Flaviviridae, Bunyaviridae and Reoviridae). The recent outbreak of infection with Zika virus (ZIKV, Flaviviridae) in human beings has brought increased attention to previously this neglected arboviruses. The replication of several flaviviruses, including DENV and alphaviruses (CHIKV), is dependent on continuous synthesis of fatty acids; the use of chemicals to inhibit their production has been shown to decrease virus production
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