Simkin M, Shohat G, Teitz Y, Margalith M; International Conference on Antiviral Research.
Antiviral Res. 1998 Mar; 37: 13 (abstract no. 204).
Department of Virology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Cytomegalovirus (CMV) may cause severe localized or disseminated life-threatening diseases in organ transplant patients and AIDS patients. The currently available antiviral drugs ganciclovir and foscarnet, have toxic side effects and clinical CMV resistance emerges. The aim of this study is to provide new non-cytotoxic and efficient anti-CMV drugs. Newly synthesized two Thiosemicarbazone derivatives (TSCDs) were chosen since they have minimal effects on cell growth in culture and on cellular protein synthesis. Human foreskin fibroblasts (HFF) and engineered human osteosarcoma cells (HOS-HXG) which contain a defective HIV-1 provirus genome were used. CMV (Towne strain) antigens were measured in the infected cells by immunoperoxidase (IPA) and immunofluorescence (IFA) assays and infectious CMV in the culture supernatant fluid was measured by titrations on HFF cells. HIV-1 p24 antigen was detected by enzyme linked immunosorbent assay (ELISA). The two TSCDs compounds at non-cytotoxic concentrations showed inhibitory effect on CMV antigens production as tested by IPA six days after infection and treatment. The first derivative at 8 micrograms/ml inhibited antigens synthesis in 93% CMV of HFF cells and at 2 micrograms/ml in 67% of HOS-HXG cells, and also inhibited CMV infectivity. The same concentration which inhibited CMV replication had no inhibitory effect on HIV-1 p24 antigen level in HOS-HXG cells. This may suggest that this HIV-1 p24, in HOS-HXG cells, has a cellular and not a viral promoter. Preliminary results with the second derivative also showed inhibitory effect on CMV antigens and infectivity and no inhibitory effect on HIV-1 p24 antigen. The parental drug M-IBT, which inhibited pox viruses, had no effect on CMV replication and HIV-1 p24 synthesis. The development of alternative anti-CMV drugs is important. Further studies are needed in order to establish the TSCDs as anti-CMV drugs for treatment.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Antigens, Viral
- Antiviral Agents
- Cytomegalovirus
- Cytomegalovirus Infections
- Cytomegalovirus Retinitis
- Enzyme-Linked Immunosorbent Assay
- Foscarnet
- Ganciclovir
- HIV-1
- Humans
- Immunoenzyme Techniques
- Proviruses
- Research
- Thiosemicarbazones
- immunology
- transplantation
Other ID:
UI: 102236656
From Meeting Abstracts