In vitro inhibition of HIV-1 by Met-SDF-1beta alone or in combination with antiretroviral drugs.
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.
Rusconi
S
S
Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, USA. rusconi@mailserver.unimi.it
Merrill
D P
DP
La Seta Catamancio
S
S
Citterio
P
P
Bulgheroni
E
E
Croce
F
F
Chou
T C
TC
Yang
O O
OO
Herrmann
S H
SH
Galli
M
M
Hirsch
M S
MS
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*
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