Fig. 1: F13 forms a homodimer that can be inserted into a membrane’s surface.

a, Schematic representation of the replication cycle of OPXVs. Mature viruses enter the cell, fusing their membrane (in blue) with the cellular one. After DNA replication, immature particles are formed (IV, membrane in red), which give rise to intracellular mature virus particles in the cytoplasm of the infected cell. Mature viruses (MV) can either be released by lysis or wrapping. In the latter, mature viruses acquire two additional membranes (WV, in orange) from the Golgi apparatus or endosomal vesicles to form wrapped virions, fuse the outermost with the plasma membrane and release enveloped viruses (EV). Tecovirimat blocks wrapping, as indicated. The scheme, adapted from Fig. 1 in ref. ⁸⁶, was created with BioRender.com. b, Crystal structure of the sF13 homodimer represented in cartoon. One protomer is coloured blue and the other green. The N termini and the MIR are indicated on one protomer, and the phospholipase active site is indicated on the other. Bottom panels provide close-up views of the two regions forming the dimer interface, indicated by coloured rectangles in the upper panel. All single escape mutants identified to date are shown as spheres, coloured according to their potency, reported as IC50 fold change. c, Side view of the F13 homodimer interacting with a lipid membrane that mimics Golgi membrane composition, as observed from molecular dynamics simulations. For clarity, water molecules and lipids in the foreground of the membrane are not shown. sF13 chains are coloured as in b, with palmitoylated cysteines and hydrophobic residues in the MIR and N termini depicted as sticks. The bottom panel provides close-up views to show lipid–protein interactions, with the protein residues involved in the interaction depicted as sticks and labelled. Protein carbons are coloured according to the chain, membrane carbons in white. Nitrogen, oxygen, sulfur and phosphate atoms are coloured blue, red, yellow and orange, respectively.