Molecular targeting for treatment of human T-lymphotropic virus type 1 infection

The Design of Novel Kni-10729 Based Compound for Inhibition of HTLV-1 Protease as Novel Insight for Development of Anti-HTLV Drugs

“…Three-dimensional structures of HTLV-1 and HIV proteases, are relatively (approximately 38%) similar to each other. Therefore, it was expected that, HIV anti-protease drugs could be inhibited HTLV-1 protease, which this hypothesis has been proven in in-vivo experiments, too (6,7). In our study, the binding affinity ratio of Indinavir (as FDA approved drug) to active site of HTLV-1 protease was -11.3 kcal mol -1 .…”

“…According to related studies, HTLV-1 protease is a homodimer protein, each chain (A and B) consisting of 125 residues. Synthetic molecules that occupy the active site of enzyme, can be considered as HTLV-1 anti-protease drugs (6). In the present study, affinity of 14 different compounds was evaluated for occupation of active site of enzyme; based on results, Kni-10729-derived inhibitor (-12) ( Figure 2) and Peptidomimetic Arg-Arg:F (-5.8) have the highest and lowest affinity with protease active site respectively.…”

Curcumin as an Herbal Inhibitor Candidate Against HTLV-1 Protease

“…Thus, owing to the lack of selective specificity, several anti-viral components (e.g. Lamivudine) have been rejected by HTLV-1 (7,8).…”

“…Although more than 90% of infected cases are as asymptomatic carriers, approximately 2% -6% of cases develop to the Adult T cell leukemia/lymphoma (ATLL). Also, 2% -3% of cases progress to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (8,9).…”

“…The retroviruses have encoded three enzymes, protease (PR), reverse transcriptase (RT) and integrase (IN), which are responsible for viral replication and retroviral pathogenesis (8). Similar to the HIV protease, HTLV-1 protease is a homodimer protein and each subunit is composed of 99 amino acids.…”