Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: An Antiviral Compound That Acts against Flaviviruses through the Inhibition of Furin-Mediated prM Cleavage
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Date
2019-11
Open Access Location
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI (Basel, Switzerland)
Rights
(c) 2019 The Author/s
CC BY 4.0
CC BY 4.0
Abstract
Flaviviruses, such as Zika virus (ZIKV), Japanese encephalitis virus (JEV), Dengue virus (DENV), and West Nile virus (WNV), are important arthropod-borne pathogens that present an immense global health problem. Their unpredictable disease severity, unusual clinical features, and severe neurological manifestations underscore an urgent need for antiviral interventions. Furin, a host proprotein convertase, is a key contender in processing flavivirus prM protein to M protein, turning the inert virus to an infectious particle. For this reason, the current study was planned to evaluate the antiviral activity of decanoyl-Arg-Val-Lys-Arg-chloromethylketone, a specific furin inhibitor, against flaviviruses, including ZIKV and JEV. Analysis of viral proteins revealed a significant increase in the prM/E index of ZIKV or JEV in dec-RVKR-cmk-treated Vero cells compared to DMSO-treated control cells, indicating dec-RVKR-cmk inhibits prM cleavage. Plaque assay, qRT-PCR, and immunofluorescence assay revealed a strong antiviral activity of dec-RVKR-cmk against ZIKV and JEV in terms of the reduction in virus progeny titer and in viral RNA and protein production in both mammalian cells and mosquito cells. Time-of-drug addition assay revealed that the maximum reduction of virus titer was observed in post-infection treatment. Furthermore, our results showed that dec-RVKR-cmk exerts its inhibitory action on the virus release and next round infectivity but not on viral RNA replication. Taken together, our study highlights an interesting antiviral activity of dec-RVKR-cmk against flaviviruses.
Description
Keywords
Japanese encephalitis virus, Zika virus, flavivirus, furin inhibitor, precursor membrane protein, Amino Acid Chloromethyl Ketones, Animals, Antiviral Agents, Cell Line, Chlorocebus aethiops, Encephalitis Virus, Japanese, Flavivirus, Furin, Vero Cells, Viral Envelope Proteins, Virus Release, Virus Replication, Zika Virus
Citation
Imran M, Saleemi MK, Chen Z, Wang X, Zhou D, Li Y, Zhao Z, Zheng B, Li Q, Cao S, Ye J. (2019). Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: An Antiviral Compound That Acts against Flaviviruses through the Inhibition of Furin-Mediated prM Cleavage.. Viruses. 11. 11. (pp. E1011-).