In vitro Evaluation of Anti-Human Immunodeficiency Virus Activity of Nucleoside Derivatives and Studies on Their Mode of Action

ABSTRACT

To evaluate in vitro anti-HIV efficacies of nucleoside derivatives, MT-4 cell line was infected with HIV-1 and HIV-2 respectively and treated with various compounds and the formerly approved drugs such as AZT, d4T, ddC and ddI. CPE method was used to evaluate their antiviral activity Most dideoxynucleosides, AZT, d4T, ddC and ddI, showed anti-HIV activities against both viruses but no other compounds including anti-herpesvirus drugs did any. Further experiments were carried out to study their inhibitory mechanism of viral adsorption. The results showed no inhibition of syncytium formation due to an interaction between the gp120 expressed in HIV-infected cell surface and CD4 receptor on the uninfected cell surface in the presence of AZT. AZT showed no activity up to 100 microgram/ml. Inhibition of reverse transcriptase (RT) in the presence of AZT-triphosphate was tested by using RT expressed in E. coli and purified and its IC50 was 4.5 nM.