The Indinavir Derivate as a Novel Pharmacophore for Treatment of HTLV-1 Viral Infections

Human T-lymphotropic virus type 1 (HTLV-1), is as a type C retrovirus, which was first isolated from a patient with Adult T-cell leukemia/lymphoma (ATLL). Approximately 10-20 million people are infected by HTLV-1 virus worldwide, but only 5-10% of them develop clinical manifestations such as Acute-T lymphoma (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), uveitis, and infective dermatitis. Indinavir was the first protease inhibitor used for treating HIV-1. It has some activity on HTLV-1, but it is not fully able to inhibit the HTLV-1 protease. Nowadays, design and construction of novel pharmacophore compounds can serve as an appropriate replacement for Indinavir. 

In the present research, we used bioinformatics studies, to evaluate the potential role of four novel pharmacophres with inhibitory function on HTLV-1 protease, so called KMI pharmacophores (Keikha Modified Indinavir).

After a detailed structural analysis of each of them, it seems all four designed phamacophores, (especially KMI-3) could be more effective on HTLV-1 protease than Indinavir.

According to exact in silico evaluations of each four pharmacophores, KMI-3 demonstrated a potential for its use on treatment of HTLV-1 infections.