Extended Data Fig. 10: Inhibitor susceptibility determinants and modeling of neutralizing antibody- and receptor-bound JUNV and MACV GPC structures.
From: Molecular organization of the New World arenavirus spike glycoprotein complex
a, JUNV GPC model indicating sites of substitutions previously shown to result in resistance to ST-193 or ST-294, two chemically unrelated small molecule inhibitors of pH-dependent membrane fusion that target SSP-GP2 interactions to inhibit membrane fusion19,47,48,54. Cα atoms at the location of substituted residues are shown as either green (SSP) or magenta (GP2) spheres for one of the SSP and GP2 protomers. Dashed lines indicate the relative position of the viral membrane. b, Superposition of JUNV GPC with the crystal structure of JUNV GP1 bound to the Fab of a non-neutralizing antibody, CR1-10 (5W1K)20. Residues that contact each other during trimerization at the GP1 apex are shown as yellow spheres and indicated (see also Fig. 3c). These residues are also within the footprint of CR1-10. c,d, Superposition of JUNV GPC with the crystal structure of JUNV GP1 bound to Fabs from neutralizing antibodies GD01 (PDB: 5EN2)20 (c) or CR1-28 (PDB: 5W1K)20 (d). e,f, Superposition of MACV GPC with the crystal structure of MACV GP1 bound to a monomer of the TfR1 ectodomain (PDB: 3KAS)27 (e) or to the Fab of neutralizing CR1-07 (PDB: 5W1M)20 (f).
