Suppression of HIV-1 Replication by a 4-H-Quinolizine Derivative

Abstract

A novel derivative of 4-H-quinolizine, 3-cyano-1-ethoxycarbonyl-4-imino-2-isopropyl-4-H-quinolizine (KAV-397), was discovered to inhibit replication of human immunodeficiency virus type 1 (HIV-1) in T-lymphocyte cell lines. HIV-infected T cells proliferated at the same growth rate as uninfected cells for at least 8 days when the cells were co-cultivated with KAV-397, while infected control cells died in 3 or 4 days. This compound inhibited reverse transcriptase (RT) activity of HIV-1 but did not compete with either deoxythymidine triphosphate substrates nor template-primers. It had no or little effect on RT activities of HIV-2, avian leukosis virus (ALV) and murine leukaemia virus (MuLV). Regarding eukaryotic DNA-dependent DNA polymerases, it significantly suppressed chicken DNA polymerase α and slightly suppressed γ but not murine DNA polymerase β.