title: 2´,3´-Dialdehyde of ATP, ADP, and adenosine inhibit HIV-1 reverse transcriptase and HIV-1 replication.
abstract: The 2´3´-dialdehyde of ATP or oxidized ATP (oATP) is a compound known for specifically making covalent bonds with the nucleotide-binding site of several ATP-binding enzymes and receptors. We investigated the effects of oATP and other oxidized purines on HIV-1 infection and we found that this compound inhibits HIV-1 and SIV infection by blocking early steps of virus replication. oATP, oxidized ADP (oADP), and oxidized Adenosine (oADO) impact the natural activity of endogenous reverse transcriptase enzyme (RT) in cell free virus particles and are able to inhibit viral replication in different cell types when added to the cell cultures either before or after infection. We used UFLC-UV to show that both oADO and oATP can be detected in the cell after being added in the extracellular medium. oATP also suppresses RT activity and replication of the HIV-1 resistant variants M184V and T215Y. We conclude that oATP, oADP and oADO display anti HIV-1 activity that is at in least in part due to inhibitory activity on HIV-1 RT.
authors.forename: Julieta
authors.initials: J
authors.lastname: Schachter
authors.forename: Ana Luiza Chaves
authors.initials: AL
authors.lastname: Valadao
authors.forename: Renato Santana
authors.initials: RS
authors.lastname: Aguiar
authors.forename: Victor
authors.initials: V
authors.lastname: Barreto-de-Souza
authors.forename: Atila Duque
authors.initials: AD
authors.lastname: Rossi
authors.forename: Pablo Ricardo
authors.initials: PR
authors.lastname: Arantes
authors.forename: Hugo
authors.initials: H
authors.lastname: Verli
authors.forename: Paula Gabriela
authors.initials: PG
authors.lastname: Quintana
authors.forename: Norton
authors.initials: N
authors.lastname: Heise
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.forename: Dumith Chequer
authors.initials: DC
authors.lastname: Bou-Habib
authors.affiliation: Instituto de Biofísica, Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Polo de Xerem, RJ, Brasil. julieta@biof.ufrj.br.
authors.forename: Pedro Muanis
authors.initials: PM
authors.lastname: Persechini
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; C017199:2',3'-dialdehyde ATP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000241:Adenosine