(A) The known domains of GP2 are color-coded: NFP (red); IFL (orange); HR1 (yellow); T-loop (green); HR2 (blue); MPER (purple); TM (black); cytoplasmic tail (gray). (B) Cartoon representation of the pre-fusion crystal structure of a GP2 monomer (PDB: 5VK2). (C) Sequence alignment of the NFP and IFL of pathogenic and/or OW arenaviruses with numbering according to the LASV sequence. Pathogenic arenaviruses are denoted via **. The prototypic Pichinde virus is also shown. Residues with full conservation are indicated by an asterisk (*), whereas those with strongly and weakly similar properties are shown via a semicolon (:) and period (.), respectively. Abbreviations: CHAVB, Chapare virus; DNDV, Dandenong virus; GTOV, Guanarito virus; IPPYV, Ippy virus; LUJOV, Lujo virus; MACV, Machupo virus; MOBV, Mobala virus; MOPV, Mopeia virus; PICV, Pichinde virus; SABV, Sabia virus; WWAV, Whitewater Arroyo virus.