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dc.contributor.authorMichailidis, Eleftherioseng
dc.contributor.authorMarchand, Brunoeng
dc.contributor.authorKodama, Eiichi N.eng
dc.contributor.authorSingh, Kamlendraeng
dc.contributor.authorKirby, Karen, 1979-eng
dc.contributor.authorOng, Yee T.eng
dc.contributor.authorRyan, Emily M.eng
dc.contributor.authorNagy, Evaeng
dc.contributor.authorAshida, Noriyukieng
dc.contributor.authorMurphey-Corb, Mickeyeng
dc.contributor.authorMitsuya, Hiroakieng
dc.contributor.authorParniak, Michael A.eng
dc.contributor.authorSarafianos, Stefan G.eng
dc.contributor.corporatenameUniversity of Missouri (System)eng
dc.contributor.meetingnameMissouri Life Sciences Summit (2010: University of Missouri--Kansas City)eng
dc.date.issued2010-02eng
dc.descriptionComparative Medicine - OneHealth and Comparative Medicine Poster Sessioneng
dc.description.abstractThe nucleoside 4'-ethynyl-2-fluoro-deoxyadenosine (EFdA) is one of the most potent antiretroviral nucleosides yet described, inhibiting replication of wild-type and multidrug-resistant HIV-1 strains in vitro (PBMC cells) with an EC50 as low as 50 pM. Our laboratory works in collaboration with academic, government and pharmaceutical industry laboratories, to characterize the mechanism of action of EFdA, and help develop it as a therapeutic for the treatment of HIV-infected patients, and as a topical microbicide to minimize sexual transmission of HIV. We have recently shown that the potency of antiviral activity stems in part from a mechanism of action not shown by any of the clinically used nucleoside antiretrovirals. Unlike other Reverse Transcriptase (RT) inhibitors, EFdA has a 3'-OH group which is necessary for nucleotide incorporation, yet it acts as a chain-terminator of retroviral DNA synthesis. Using biochemical techniques, we have determined that EFdA is incorporated very efficiently into the nascant viral DNA chain and blocks the incorporation of incoming nucleotides by stopping the translocation/movement of RT. Therefore, we have dubbed EFdA as a Translocation-Defective RT Inhibitor (TDRTI). A pilot collaborative study spearheaded by collaborators Parniak and Corb demonstrated that EFdA treatment of Rhesus Macaques resulted in a 2-3 log decrease in simian immunodeficiency virus (SIV) within seven days; these levels declined to undetectable levels (5-log reduction) within 2 months and essentially remained so for the duration of therapy. Hence, EFdA is a highly potent HIV RT inhibitor with in vitro and in vivo antiviral activities that warrant further development of the compound as a potential therapeutic for individuals harboring wild-type and/or multi-drug resistant HIV-1.eng
dc.identifier.urihttp://hdl.handle.net/10355/6194eng
dc.languageEnglisheng
dc.relation.ispartofAbstracts (Missouri Regional Life Sciences Summit 2010)eng
dc.relation.ispartofcommunityUniversity of Missouri System. Missouri Summits. Missouri Regional Life Sciences Summit 2010eng
dc.subjectantiretroviral nucleosideseng
dc.subjectdrug resistanceeng
dc.subjectsexual transmissioneng
dc.subject.lcshAntiretroviral agentseng
dc.subject.lcshDrug resistanceeng
dc.subject.lcshSexually transmitted diseaseseng
dc.titleInhibition Mechanism of EFdA, a Highly Potent Inhibitor of HIV Reverse Transcriptase [abstract]eng
dc.typeAbstracteng


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