bictegravir and HTLV-I-Infections

Between 10 and 20 million people worldwide are infected with the human T-cell lymphotropic virus type 1 (HTLV-1). Despite causing life-threatening pathologies there is no therapeutic regimen for this deltaretrovirus. Here, we screened a library of integrase strand transfer inhibitor (INSTI) candidates built around several chemical scaffolds to determine their effectiveness in limiting HTLV-1 infection. Naphthyridines with substituents in position 6 emerged as the most potent compounds against HTLV-1, with XZ450 having highest efficacy in vitro. Using single-particle cryo-electron microscopy we visualised XZ450 as well as the clinical HIV-1 INSTIs raltegravir and bictegravir bound to the active site of the deltaretroviral intasome. The structures reveal subtle differences in the coordination environment of the Mg

Topics: Amides; Antiviral Agents; Catalytic Domain; Cryoelectron Microscopy; Deltaretrovirus; Drug Resistance, Viral; Heterocyclic Compounds, 3-Ring; HIV Integrase; HIV-1; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Naphthyridines; Piperazines; Pyridones; Recombinant Proteins