title: In vitro inhibition of HIV-1 by Met-SDF-1beta alone or in combination with antiretroviral drugs.
abstract: Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor-1 (SDF-1), Met-SDF-1beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 microg/ml range for Met-SDF-1beta. Met-SDF-1beta showed synergy to additivity with either zidovudine or nelfinavir at IC75 IC90 and IC95. Additivity was seen when Met-SDF-1beta was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies.
authors.affiliation: Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, USA. rusconi@mailserver.unimi.it
authors.forename: S
authors.initials: S
authors.lastname: Rusconi
authors.forename: D P
authors.initials: DP
authors.lastname: Merrill
authors.forename: S
authors.initials: S
authors.lastname: La Seta Catamancio
authors.forename: P
authors.initials: P
authors.lastname: Citterio
authors.forename: E
authors.initials: E
authors.lastname: Bulgheroni
authors.forename: F
authors.initials: F
authors.lastname: Croce
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: O O
authors.initials: OO
authors.lastname: Yang
authors.forename: S H
authors.initials: SH
authors.lastname: Herrmann
authors.forename: M
authors.initials: M
authors.lastname: Galli
authors.forename: M S
authors.initials: MS
authors.lastname: Hirsch
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019888:Nelfinavir / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D018894:Reverse Transcriptase Inhibitors; C119139:methionine stromal cell-derived factor-1beta; D015215:Zidovudine; D008715:Methionine; D019888:Nelfinavir