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A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis

Zoonotic coronavirus infections, such as those responsible for the current SARS-CoV-2 pandemic, cause grave international public health concern. In infected cells, the coronavirus RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle. Although double-membrane vesicles appear to be an element of replication organelles across all coronaviruses, studies to date describe an assortment of additional coronavirus-induced membrane structures. Despite much speculation, it remains unclear which replication organelle element(s) actually accommodate viral RNA synthesis. Snijder et al. provide detailed 2D and 3D analyses of replication organelles and show that diverse coronaviruses essentially induce the same membrane modifications. These results provide a unifying model of the coronavirus replication organelle and clearly establish double-membrane vesicles as the central hub for viral RNA synthesis and a potential drug target in coronavirus infection. The image shows a surface-rendered model of a representative area of a tomogram containing the different types of MERS-CoV-induced membrane modifications: convoluted membranes (blue), double-membrane spherules (orange), and double-membrane vesicles (yellow and lilac, outer and inner membranes, respectively). The model also highlights endoplasmic reticulum membranes (green) and a vesicle (silver) containing new virions (pink).

Image Credit: Ronald Limpens

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