Combating HTLV-1 infections with Taxus baccata phytoconstituents: Molecular mechanisms potential anti-ATLL agents

Abstract

Taxus baccata is recognized as a traditional herb with antiviral and anticancer properties, making it a valuable candidate for anti-proliferative and antiviral agents, particularly in the absence of a cure for HTLV-1 infection and related diseases. The alkaloid extract of Taxus baccata was evaluated for its impact on HTLV-1-MT2 cell proliferation and HTLV-1 protease activity, presenting a promising avenue for therapeutic applications akin to HIV-PR inhibitors. Given the pressing need for effective treatments for HTLV-1-associated conditions, our study delved into the alkaloid extract's effects through immunofluorescence assays on HTLV-1 protease both in vitro and in silico. Confirmation of Taxus baccata extraction was achieved through immunofluorescence, infrared spectroscopy (IR), gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC) analysis, with paclitaxel serving as a control. Furthermore, the anticancer properties of the alcoholic and alkaloid extracts were explored through in vitro assays using various cell lines, including HTLV-1-MT2, A549, HT29, and MCF7, alongside flow cytometry assessments. Notably, treatment with the alkaloid extract significantly impacted the survival of HTLV-1-MT2 cells (-2.44±0.012), alcoholic extract (11.17$\pm 0.13$) and paclitaxel (0.00$\pm 0.18$) were evaluated. GC-MS analysis identified Dimethyl malate, Lichexanthone, and Glycinexylidide as bioactive compounds within the plant, with investigations into their molecular interactions with HTLV-1 protease conducted. Molecular dynamics studies revealed key interaction sites between the compounds and HTLV-1 protease (PDB ID:4YDF), particularly highlighting the binding sequence of the dimethyl malate ligand within the protease A chain (Ala59). Collectively, the alkaloid compounds from Taxus baccata exhibit potential inhibitory effects on HTLV-1 oncovirus proliferation and transmission.