Abstract
Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 ± 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.
Highlights
Flaviviruses are small, enveloped, single-stranded positive-sense RNA viruses that cause serious diseases in humans and animals [1,2]
We have previously identified and optimized anti-adenoviral compounds resulting in benzavir-2 (Figure 1A), a novel antiviral compound with broad antiviral activity against both DNA viruses, human adenovirus (HAdV) [16,17], herpes simplex virus type 1 and type 2 (HSV-1, HSV-2) [18], and, recently, RNA virus, and rift valley fever virus (RVFV) [19]
To explore the anti-Zika virus (ZIKV) activity of benzavir-2, we assessed the inhibition of Zoanthus species green fluorescence protein (ZsGreen) expression after infection of the recombinant ZIKV
Summary
Flaviviruses are small, enveloped, single-stranded positive-sense RNA viruses that cause serious diseases in humans and animals [1,2]. Most flaviviruses are arthropod-borne viruses transmitted to vertebrate hosts by either mosquitoes or ticks [3]. Several members of the flavivirus genus, such as the Zika virus (ZIKV), dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV), are highly pathogenic to humans [4,5,6]. The recent outbreaks of flaviviruses have raised a global concern, since several reports linked the recent ZIKV outbreak in the Americas with an increase of microcephaly cases in fetuses and newborns and an increase of Guillian–Barre syndrome cases [7,8,9]. Flaviviruses pose a global threat to the population, Viruses 2020, 12, 351; doi:10.3390/v12030351 www.mdpi.com/journal/viruses
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