Anti-HIV-1 activity in vitro of ceftazidime degradation products.
Cephalosporins in aqueous solutions generate degradation products that inhibit in vitro HIV-1 replication in cell lines, as well as in primary cells (lymphocytes and macrophages). This effect is observed at concentrations that do not interfere with the normal functions of these cells. Upon chromatographic fractionation of an aqueous solution of hydrolysed ceftazidime, a high molecular weight fraction (MW 8000) with antiviral activity was isolated. The exact chemical nature of the active component responsible for the anti-HIV activity in vitro appears to be complex and is currently unknown. Inhibition of HIV-1 reverse transcriptase and RNase H activity was observed, however, higher concentrations than those needed to inhibit HIV replication were required. The inhibitory action of the hydrolysed ceftazidime was manifested during the early phase of the HIV-1 life-cycle. Despite a lack of a direct effect of the CD4/gp120 interaction, HIV-1 mediated cell fusion was inhibited by the hydrolysed ceftazidime, suggesting that the active principle acts in a very early stage of the viral life-cycle.
Hobi
R
R
Institute of Veterinary Biochemistry, University of Zürich-Irchel, Zürich, Switzerland. hobi@vetbio.unizh.ch
Hübscher
U
U
Neftel
K
K
Alteri
E
E
Poncioni
B
B
Walker
M R
MR
Woods-Cook
K
K
Schneider
P
P
Lazdins
J K
JK
D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism; D002442:Ceftazidime / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008970:Molecular Weight; D011485:Protein Binding; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D002442:Ceftazidime; D054303:HIV Reverse Transcriptase; D004259:DNA-Directed DNA Polymerase