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@ARTICLE{Chen:278658,
author = {Chen, Yuexuan and Klute, Susanne and Sparrer, Konstantin
Maria Johannes and Serra-Moreno, Ruth},
title = {{RAB}5 is a host dependency factor for the generation of
{SARS}-{C}o{V}-2 replication organelles.},
journal = {mBio},
volume = {16},
number = {5},
issn = {2161-2129},
address = {Washington, DC},
publisher = {American Society for Microbiology},
reportid = {DZNE-2025-00614},
pages = {e0331424},
year = {2025},
abstract = {Severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) remains a threat due to the emergence of
variants with increased transmissibility and enhanced escape
from immune responses. Like other coronaviruses before,
SARS-CoV-2 likely emerged after its transmission from bats.
The successful propagation of SARS-CoV-2 in humans might
have been facilitated by usurping evolutionarily conserved
cellular factors to execute crucial steps in its life cycle,
such as the generation of replication organelles-membrane
structures where coronaviruses assemble their
replication-transcription complex. In this study, we found
that RAB5, which is highly conserved across mammals, is a
critical host dependency factor for the replication of the
SARS-CoV-2 genome. Our results also suggest that SARS-CoV-2
uses RAB5+ membranes to build replication organelles with
the aid of COPB1, a component of the COP-I complex, and that
the virus protein NSP6 participates in this process. Hence,
targeting NSP6 represents a promising approach to interfere
with SARS-CoV-2 RNA synthesis and halt its
propagation.IMPORTANCEIn this study, we sought to identify
the host dependency factors that severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) uses for the generation
of replication organelles: cellular membranous structures
that SARS-CoV-2 builds in order to support the replication
and transcription of its genome. We uncovered that RAB5 is
an important dependency factor for SARS-CoV-2 replication
and the generation of replication organelles, and that the
viral protein NSP6 participates in this process. Hence, NSP6
represents a promising target to halt SARS-CoV-2
replication.},
keywords = {Humans / rab5 GTP-Binding Proteins: metabolism / rab5
GTP-Binding Proteins: genetics / Virus Replication /
SARS-CoV-2: physiology / SARS-CoV-2: genetics / Animals /
COVID-19: virology / Host-Pathogen Interactions / Vero Cells
/ Chlorocebus aethiops / Viral Replication Compartments:
metabolism / COP-I (Other) / COPB1 (Other) / NSP6 (Other) /
RAB5 (Other) / SARS-CoV-2 (Other) / replication organelle
(Other) / rab5 GTP-Binding Proteins (NLM Chemicals) / RAB5C
protein, human (NLM Chemicals)},
cin = {AG Sparrer},
ddc = {570},
cid = {I:(DE-2719)1910003},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40167317},
pmc = {pmc:PMC12077180},
doi = {10.1128/mbio.03314-24},
url = {https://pub.dzne.de/record/278658},
}