Human Immunodeficiency Virus Type 1 Tat and Rev as Potential Targets for Drug Development

摘要: This chapter discusses the potential of HIV Tat, Rev, and their cellular cofactors as drug targets. Tat interacts with numerous transcriptional regulatory factors presumably by virtue its interaction transcription activation response (TAR) RNA, recruits these to human immunodeficiency virus type 1 (HIV-1) promoter. Thus, HIV-1 directed from viral long terminal repeat (LTR) is balanced actions kinases phosphatases, both can be targets for development. promotes elongation transcripts increasing occupancy time CDK9/cyclin T1 on LTR. Small-molecule inhibitors Tat-TAR RNA interaction, small-molecule CDKs such CDK9 or CDK2, that disrupt additional host cell p300/CREB binding protein-associated factor (PCAF) and/or inhibit activities could all viable anti-HIV candidates. Both TAR are essential activated transcription, were thus first candidates considered design targeted transcription. Antiviral development against proteins Rev represents a conceptual work in progress. In arena inhibiting cofactors, concerns over toxicity have not been fully resolved. Future efforts needed address two major challenges mechanistic specificity functional toxicity.