Evidence map›Paper›PMID 32511245›Full record

ArticlePLoS biology2020

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

Eric J Snijder, Ronald W A L Limpens, Adriaan H de Wilde, Anja W M de Jong, Jessika C Zevenhoven-Dobbe, Helena J Maier, Frank F G A Faas, Abraham J Koster, Montserrat Bárcena

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 338 papers.

0numbers the graph read from it
0cells of the map it votes in
338citing papers in PubMed
9.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

338 citing papers in PubMed, 469 citations in OpenAlex.

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  12. Insights into SARS-CoV-2 replication controlActa pharmaceutica Sinica. B · 2026
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278 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Eric J SnijderMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0003-3297-2309
Ronald W A L LimpensSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0002-6243-6729
Adriaan H de WildeMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
Anja W M de JongSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0001-8110-8520
Jessika C Zevenhoven-DobbeMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
Helena J MaierThe Pirbright Institute, Pirbright, Surrey, United Kingdom.
Frank F G A FaasSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0002-1774-700X
Abraham J KosterSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0003-1717-2549
Montserrat BárcenaSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0002-7719-4443
Leiden University Medical Center · NLThe Pirbright Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BBS/E/I/00007034Biotechnology and Biological Sciences Research Council BBS/E/I/COV07001
6 · The paper itself

Abstract

Zoonotic coronavirus (CoV) infections, such as those responsible for the current severe acute respiratory syndrome-CoV 2 (SARS-CoV-2) pandemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). Although double-membrane vesicles (DMVs) appear to be a pan-CoV RO element, studies to date describe an assortment of additional CoV-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication. Metabolic labeling of newly synthesized viral RNA followed by quantitative electron microscopy (EM) autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs Middle East respiratory syndrome-CoV (MERS-CoV) and SARS-CoV and the gamma-CoV infectious bronchitis virus. RNA synthesis could not be linked to DMSs or any other cellular or virus-induced structure. Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in CoV infection.

Indexed as

Virus ReplicationAnimalsBetacoronavirusCell LineChlorocebus aethiopsCoronavirusCoronavirus InfectionsCOVID-19Electron Microscope TomographyEndoplasmic ReticulumHumansMiddle East Respiratory Syndrome CoronavirusPandemicsPneumonia, ViralRNA, ViralSARS-CoV-2RNA, Viral

Identifiers

PMID32511245
PMCPMC7302735
OpenAlexW3033917173

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.