The human immunodeficiency virus (HIV) is the pathogen retrovirus of acquired immunodeficiency syndrome (AIDS). Currently, combination antiretroviral therapy (cART), which is a combinational dosage of several anti-HIV drugs to suppress viral replication and control the disease progression. However, due to the emergence of drug-resistant strains of HIV, significant side effect and high costs, novel anti-HIV-1 drugs with different mechanisms of action are urgently needed. Targets of most clinically available anti-HIV-1 drugs are reverse-transcriptase, protease and integrase. Therefore, this study focuses on novel anti-HIV-1 agents interacting with several conserved regions of envelope proteins to develop anti-HIV-1 agents with novel mechanisms of action.

　　So far, we have developed CD4 mimics, which are dipeptide mimic derivatives derived from CD4 [1]. CD4 mimics have binding affinity for an HIV-1 envelop protein, gp120, and therefore show HIV entry inhibitory activity. In addition, our laboratory has also developed HIV-Gag-targeted compounds [2] as well as other entry and fusion inhibitors such as peptide-based coreceptor antagonists and the other envelop protein gp41-derived peptides [3]. In the case of treatment of HIV-infectious patients, a combinational dosage of three types of enzyme inhibitors against reverse transcriptase, protease and integrase is effective and shows synergistic effects. Therefore, we would like to try simultaneous usage of CD4 mimic and the other entry and fusion inhibitors including HIV-Gag-targeted compounds, which might cause an increase of anti-HIV-1 activity and their synergistic effects. Furthermore, the conjugation of these inhibitors with appropriate linkers might be desirable to exhibit the specificity.

　　In this study, we would evaluate a combinatorial usage of CD4 mimic with the other entry and fusion inhibitors including HIV-Gag-targeted compounds and develop hybrid molecules of these inhibitors.