title: Inhibition of HIV-1 infection by alkylureas.
abstract: The risk of infection by HIV-1 through transfusion of contaminated blood products has been markedly decreased but not eliminated by serological screening of donors. Methods are required to further minimize or eliminate the risk of infection of blood product recipients. We therefore examined the capacity of alkylureas to inhibit infectivity of HIV-1. Incubation of free HIV-1 virions with alkylureas suppressed their infectivity, and the minimal inhibitory concentration of the alkylureas was related to the length of the alkyl chain. Butylurea, the most potent inhibitor of HIV-1, inhibited the infectivity of 10(5) median tissue culture infective dose (TCID)50 of HIV-1, chronically HIV-1-infected H9 cells and mononuclear cells from two HIV-1-infected patients. Size fractionation of HIV-1 following incubation with butylurea indicated that the structure of the virus was disrupted by butylurea. This study demonstrates that butylurea, at a concentration that has been shown not to affect red blood cell function, can inhibit infectivity of extracellular and intracellular HIV-1. Since the HIV-1 inhibitory capacity of the alkylureas increases with the length of the alkyl side chain, it is likely that hydrophobic interactions between the alkylureas and HIV-1 are responsible for the observed effect.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: H
authors.initials: H
authors.lastname: Goldstein
authors.forename: M
authors.initials: M
authors.lastname: Pettoello-Mantovani
authors.forename: T R
authors.initials: TR
authors.lastname: Kollmann
authors.forename: T A
authors.initials: TA
authors.lastname: Calvelli
authors.forename: A
authors.initials: A
authors.lastname: Rubinstein
mesh_terms: D002460:Cell Line; D002845:Chromatography; D004797:Enzyme-Linked Immunosorbent Assay; D016655:HIV Core Protein p24 / Q000032:analysis; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016655:HIV Core Protein p24; C017680:propylurea; C007685:ethylurea; D014508:Urea; C006865:butylurea; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase