Identification of Novel Inhibitors of Human Immunodeficiency Virus Type 1 Replication by In Silico Screening Targeting Cyclin T1/Tat Interaction

摘要: Human immunodeficiency virus type 1 (HIV-1) transcription is essential for viral replication and the only step genome amplification. Cyclin T1 (CycT1) interacts with HIV-1 Tat transactivation-responsive (TAR) RNA, leading to activation of through hyperphosphorylation RNA polymerase II (RNAPII). Thus, CycT1/Tat/TAR interaction represents a novel target inhibition replication. In this study, we conducted in silico screening compounds targeting complex found that two structurally related (C1 C2) had high docking scores model complex. These proved inhibitory tumor necrosis factor alpha-stimulated chronically infected cells. addition, C3, derivative C1 C2, was be more potent inhibitor C3 also inhibited acutely The compound could suppress Tat-mediated long terminal repeat-driven gene expression phosphorylation RNAPII binding CycT1. Furthermore, pose defined by analyses its energy vitro antiviral activity, which indicates Tat-binding amino acids series described herein are inhibitors CycT1/Tat interaction.