1.G.8.1.5
Glycoprotein precursor, GPC, of Lujo mammarenavirus of 454 aas and 2 - 5 TMSs with 1 - 3 TMSs N-terminal and 1 TMS C-terminal. Lujo virus (LUJV) belongs to the Old World (OW) genus Mammarenavirus (family Arenaviridae), a biosafety level (BSL) 4 agent (Cao et al. 2021). A high-throughput screening of an FDA-approved drug library was conducted using pseudotype viruses bearing LUJV envelope glycoprotein (GPC) to identify inhibitors of LUJV entry. Three hit compounds, trametinib, manidipine, and lercanidipine, were identified as LUJV entry inhibitors in the micromolar range. Mechanistic studies revealed that trametinib inhibited LUJV GPC-mediated membrane fusion by targeting C410 [located in the transmembrane domain], while manidipine and lercanidipine inhibited LUJV entry by acting as calcium channel blockers. All three hits extended their antiviral spectra to the entry of other pathogenic mammarenaviruses, and all three could inhibit the authentic prototype mammarenavirus, lymphocytic choriomeningitis virus (LCMV), and could prevent infection at the micromolar level (Cao et al. 2021).