A molecular pore spans the double membrane of the coronavirus replication organelle

Wolff, Georg; Limpens, Ronald W.A.L.; Zevenhoven-Dobbe, Jessika C.; Laugks, Ulrike; Zheng, Shawn; de Jong, Anja W. M.; Koning, Roman I.; Agard, David A.; Grünewald, Kay; Koster, Abraham J.; Snijder, Eric J.; Bárcena, Montserrat

Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored micro-environment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and mRNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. Here, using cellular electron cryo-microscopy, we unveiled a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a critical role in coronavirus replication and thus constitutes a novel drug target