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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dc.citation.issue11
dc.citation.volume11
dc.contributor.authorImran M
dc.contributor.authorSaleemi MK
dc.contributor.authorChen Z
dc.contributor.authorWang X
dc.contributor.authorZhou D
dc.contributor.authorLi Y
dc.contributor.authorZhao Z
dc.contributor.authorZheng B
dc.contributor.authorLi Q
dc.contributor.authorCao S
dc.contributor.authorYe J
dc.coverage.spatialSwitzerland
dc.date.accessioned2024-01-18T18:34:43Z
dc.date.accessioned2024-07-25T06:46:14Z
dc.date.available2019-10-31
dc.date.available2024-01-18T18:34:43Z
dc.date.available2024-07-25T06:46:14Z
dc.date.issued2019-11
dc.description.abstractFlaviviruses, 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.
dc.description.confidentialfalse
dc.edition.editionNovember 2019
dc.format.paginationE1011-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/31683742
dc.identifier.citationImran 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-).
dc.identifier.doi10.3390/v11111011
dc.identifier.eissn1999-4915
dc.identifier.elements-typejournal-article
dc.identifier.issn1999-4915
dc.identifier.number1011
dc.identifier.piiv11111011
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/70835
dc.languageeng
dc.publisherMDPI (Basel, Switzerland)
dc.publisher.urihttps://www.mdpi.com/1999-4915/11/11/1011
dc.relation.isPartOfViruses
dc.rights(c) 2019 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectJapanese encephalitis virus
dc.subjectZika virus
dc.subjectflavivirus
dc.subjectfurin inhibitor
dc.subjectprecursor membrane protein
dc.subjectAmino Acid Chloromethyl Ketones
dc.subjectAnimals
dc.subjectAntiviral Agents
dc.subjectCell Line
dc.subjectChlorocebus aethiops
dc.subjectEncephalitis Virus, Japanese
dc.subjectFlavivirus
dc.subjectFurin
dc.subjectVero Cells
dc.subjectViral Envelope Proteins
dc.subjectVirus Release
dc.subjectVirus Replication
dc.subjectZika Virus
dc.titleDecanoyl-Arg-Val-Lys-Arg-Chloromethylketone: An Antiviral Compound That Acts against Flaviviruses through the Inhibition of Furin-Mediated prM Cleavage
dc.typeJournal article
pubs.elements-id435679
pubs.organisational-groupOther
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