Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0050995
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dc.titleRelease of Dengue Virus Genome Induced by a Peptide Inhibitor
dc.contributor.authorLok S.-M.
dc.contributor.authorCostin J.M.
dc.contributor.authorHrobowski Y.M.
dc.contributor.authorHoffmann A.R.
dc.contributor.authorRowe D.K.
dc.contributor.authorKukkaro P.
dc.contributor.authorHoldaway H.
dc.contributor.authorChipman P.
dc.contributor.authorFontaine K.A.
dc.contributor.authorHolbrook M.R.
dc.contributor.authorGarry R.F.
dc.contributor.authorKostyuchenko V.
dc.contributor.authorWimley W.C.
dc.contributor.authorIsern S.
dc.contributor.authorRossmann M.G.
dc.contributor.authorMichael S.F.
dc.date.accessioned2020-03-31T03:03:34Z
dc.date.available2020-03-31T03:03:34Z
dc.date.issued2012
dc.identifier.citationLok S.-M., Costin J.M., Hrobowski Y.M., Hoffmann A.R., Rowe D.K., Kukkaro P., Holdaway H., Chipman P., Fontaine K.A., Holbrook M.R., Garry R.F., Kostyuchenko V., Wimley W.C., Isern S., Rossmann M.G., Michael S.F. (2012). Release of Dengue Virus Genome Induced by a Peptide Inhibitor. PLoS ONE 7 (11) : e50995. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0050995
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/166206
dc.description.abstractDengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. The mimetic peptide, DN59, consists of residues corresponding to the membrane interacting, amphipathic stem region of the dengue virus envelope (E) glycoprotein. This peptide is inhibitory to all four serotypes of dengue virus, as well as other flaviviruses. Cryo-electron microscopy image reconstruction of dengue virus particles incubated with DN59 showed that the virus particles were largely empty, concurrent with the formation of holes at the five-fold vertices. The release of RNA from the viral particle following incubation with DN59 was confirmed by increased sensitivity of the RNA genome to exogenous RNase and separation of the genome from the E protein in a tartrate density gradient. DN59 interacted strongly with synthetic lipid vesicles and caused membrane disruptions, but was found to be non-toxic to mammalian and insect cells. Thus DN59 inhibits flavivirus infectivity by interacting directly with virus particles resulting in release of the genomic RNA.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectglycoprotein
dc.subjecthemoglobin
dc.subjectprotein inhibitor
dc.subjectribonuclease
dc.subjectRNA
dc.subjectvirus protein
dc.subjectarticle
dc.subjectcryoelectron microscopy
dc.subjectDengue virus
dc.subjectdensity gradient
dc.subjectFlavivirus
dc.subjecthemoglobin blood level
dc.subjectincubation time
dc.subjectlipid vesicle
dc.subjectnonhuman
dc.subjectpolymerase chain reaction
dc.subjectsensitivity analysis
dc.subjectserotype
dc.subjectvirus genome
dc.subjectvirus particle
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectAntiviral Agents
dc.subjectCell Line
dc.subjectCentrifugation, Density Gradient
dc.subjectDengue Virus
dc.subjectGenome, Viral
dc.subjectHumans
dc.subjectLipid Bilayers
dc.subjectMolecular Sequence Data
dc.subjectPeptides
dc.subjectViral Envelope Proteins
dc.subjectVirion
dc.subjectDengue virus
dc.subjectFlavivirus
dc.subjectHexapoda
dc.subjectMammalia
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.pone.0050995
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue11
dc.description.pagee50995
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