Anti-HIV-1 Activity in Vitro of Ceftazidime Degradation Products

• Published in: Antiviral chemistry & chemotherapy Vol. 12; no. 2; pp. 109 - 118
• Main Authors: Hobi, Reinhard, Hübscher, Ulrich, Neftel, Klaus, Alteri, Enrica, Poncioni, Bernard, Walker, Maja R, Woods-Cook, Kathie, Schneider, Peter, Lazdins, Janis K
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.03.2001; International Medical Press; Sage Publications Ltd
• Subjects: Anti-HIV Agents - chemistry; Anti-HIV Agents - metabolism; Anti-HIV Agents - pharmacology; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Biological and medical sciences; CD4 antigen; CD4 Antigens - metabolism; Ceftazidime; Ceftazidime - chemistry; Ceftazidime - metabolism; Ceftazidime - pharmacology; Cell fusion; Cell lines; Cephalosporins; Chromatography, Gel; Chromatography, High Pressure Liquid; Degradation products; DNA-Directed DNA Polymerase - metabolism; Dose-Response Relationship, Drug; Glycoprotein gp120; HIV; HIV Envelope Protein gp120 - metabolism; HIV Reverse Transcriptase - antagonists & inhibitors; HIV Reverse Transcriptase - metabolism; HIV-1 - drug effects; HIV-1 - enzymology; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Hydrolysis; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - virology; Lymphocytes; Macrophages; Medical sciences; Molecular Weight; Pharmacology. Drug treatments; Protein Binding; Replication; Ribonuclease H; RNA-directed DNA polymerase; Time Factors; Tumor Cells, Cultured; Virus Replication - drug effects; HIV-1; RNase H; ceftazidime; reverse transcriptase; cephalosporins; cell fusion; RNA-directed DNA polymerase; HIV-1 virus; Enzyme; Transferases; β-Lactams; P Glycoprotein; Retroviridae; Molecular interaction; Cell fusion; Lentivirus; In vitro; Biological activity; Virus; Nucleotidyltransferases; Cephalosporin derivatives; Antiviral; Human immunodeficiency virus; Mechanism of action; Degradation product; Ceftazidime
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.1177/095632020101200204

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.