Journal
VIRUSES-BASEL
Volume 11, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/v11111011
Keywords
flavivirus; Zika virus; Japanese encephalitis virus; furin inhibitor; precursor membrane protein
Categories
Funding
- National Key Research and Development Program of China [2016YFD0500407]
- National Natural Science Foundation of China [31825025, 31572517, 31972721]
- Fundamental Research Funds for the Central Universities [2662018QD025]
- Natural Science Foundation of Hubei Province [2019CFA010]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available