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2021-07-13Zeitschriftenartikel
Mathematical Modelling of the Molecular Mechanisms of Interaction of Tenofovir with Emtricitabine against HIV
dc.contributor.authorIannuzzi, Sara
dc.contributor.authorvon Kleist, Max
dc.date.accessioned2022-02-02T08:15:32Z
dc.date.available2022-02-02T08:15:32Z
dc.date.issued2021-07-13none
dc.identifier.other10.3390/v13071354
dc.identifier.urihttp://edoc.rki.de/176904/9330
dc.description.abstractThe combination of the two nucleoside reverse transcriptase inhibitors (NRTI) tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is used in most highly active antiretroviral therapies for treatment of HIV-1 infection, as well as in pre-exposure prophylaxis against HIV acquisition. Administered as prodrugs, these drugs are taken up by HIV-infected target cells, undergo intracellular phosphorylation and compete with natural deoxynucleoside triphosphates (dNTP) for incorporation into nascent viral DNA during reverse transcription. Once incorporated, they halt reverse transcription. In vitro studies have proposed that TDF and FTC act synergistically within an HIV-infected cell. However, it is unclear whether, and which, direct drug–drug interactions mediate the apparent synergy. The goal of this work was to refine a mechanistic model for the molecular mechanism of action (MMOA) of nucleoside analogues in order to analyse whether putative direct interactions may account for the in vitro observed synergistic effects. Our analysis suggests that depletion of dNTP pools can explain apparent synergy between TDF and FTC in HIV-infected cells at clinically relevant concentrations. Dead-end complex (DEC) formation does not seem to significantly contribute to the synergistic effect. However, in the presence of non-nucleoside reverse transcriptase inhibitors (NNRTIs), its role might be more relevant, as previously reported in experimental in vitro studies.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectNRTIeng
dc.subjectNNRTIeng
dc.subjectDECeng
dc.subjectdNTPeng
dc.subjectDDIeng
dc.subjectHIVeng
dc.subjectPrEPeng
dc.subjectintracellulareng
dc.subjectHAARTeng
dc.subjectLoeweeng
dc.subjectTFVeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleMathematical Modelling of the Molecular Mechanisms of Interaction of Tenofovir with Emtricitabine against HIVnone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/9330-1
dc.type.versionpublishedVersionnone
local.edoc.container-titleVirusesnone
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.mdpi.com/1999-4915/13/7/1354none
local.edoc.container-publisher-nameMDPInone
local.edoc.container-volume13none
local.edoc.container-issue7none
local.edoc.container-year2021none
local.edoc.container-firstpage1none
local.edoc.container-lastpage16none
dc.description.versionPeer Reviewednone

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