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2´,3´-Dialdehyde of ATP, ADP, and Adenosine Inhibit HIV-1 Reverse Transcriptase and HIV-1 Replication

[ Vol. 12 , Issue. 5 ]

Author(s):

Julieta Schachter, Ana Luiza Chaves Valadao, Renato Santana Aguiar, Victor Barreto-de-Souza, Atila Duque Rossi, Pablo Ricardo Arantes, Hugo Verli, Paula Gabriela Quintana, Norton Heise, Amilcar Tanuri, Dumith Chequer Bou-Habib and Pedro Muanis Persechini   Pages 347 - 358 ( 12 )

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.

Keywords:

HIV-1, macrophage, oxidized adenosine, oxidized ADP, oxidized ATP, reverse transcriptase.

Affiliation:

, , , , , , , , , , , Instituto de Biofísica, Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Polo de Xerem, RJ, Brasil.

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