Inhibition of human immunodeficiency virus type 1 replication and cytopathicity by synthetic soluble catecholamine melanins in vitro.
Synthetic soluble melanins were synthesized by spontaneous oxidation of L-dopamine, norepinephrine or 5-hydroxytryptamine (serotonin) in weak alkaline solution. These three melanins inhibited infection of human CD4+ lymphoblastoid cells (MT-2) by cell-free human immunodeficiency virus type 1 (HIV-1), without cell toxicity, at concentrations of 0.15-10 micrograms/ml. Also, syncytium formation and resulting cytopathic effects when uninfected cells were mixed with chronic HIV-1-infected cells were blocked by these melanins. Antisyncytial activity was greater when infected cells were preincubated with melanin than when uninfected cells were preincubated with melanin, thus suggesting that interaction of melanin with viral proteins is an important aspect of the antiviral mechanism. These results make synthetic soluble melanins interesting candidates for further study as possible anti-HIV-1 therapeutics.
Montefiori
D C
DC
Department of Pathology, Vanderbilt University Medical School, Nashville, Tennessee 37232.
Modliszewski
A
A
Shaff
D I
DI
Zhou
J
J
D002395:Catecholamines / Q000494:pharmacology*; D002459:Cell Fusion / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D008543:Melanins / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D002395:Catecholamines; D008543:Melanins