title: A new antiviral: chimeric 3TC-AZT phosphonate efficiently inhibits HIV-1 in human tissues ex vivo.
abstract: Although more-recently developed antivirals target different molecules in the HIV-1 replication cycle, nucleoside reverse transcriptase inhibitors (NRTIs) remain central for HIV-1 therapy. Here, we test the anti-HIV activity of a phosphonate chimera of two well-known NRTIs, namely AZT and 3TC. We show that this newly synthesized compound suppressed HIV-1 infection in lymphoid tissue ex vivo more efficiently than did other phosphonates of NRTIs. Moreover, the new compound was not toxic for tissue cells, thus making the chimeric phosphonate strategy a valid approach for the development of anti HIV-1 compound heterodimers.
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanpouille
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Khandazhinskaya
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Inna
authors.initials: I
authors.lastname: Karpenko
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zicari
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Victor
authors.initials: V
authors.lastname: Barreto-de-Souza
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Frolova
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States. Electronic address: margolis@helix.nih.gov.
authors.forename: Leonid
authors.initials: L
authors.lastname: Margolis
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation. Electronic address: kochet@eimb.ru.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kochetkov
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054306:Dideoxynucleotides / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D019259:Lamivudine / Q000737:chemistry / Q000494:pharmacology*; D014066:Palatine Tonsil / Q000187:drug effects* / Q000821:virology; D013942:Thymine Nucleotides / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; D019259:Lamivudine; D015215:Zidovudine; C052873:zidovudine triphosphate
keywords: Depot form; HIV-1; NRTI