%0 Journal Article
%A Chen, Yuexuan
%A Klute, Susanne
%A Sparrer, Konstantin Maria Johannes
%A Serra-Moreno, Ruth
%T RAB5 is a host dependency factor for the generation of SARS-CoV-2 replication organelles.
%J mBio
%V 16
%N 5
%@ 2161-2129
%C Washington, DC
%I American Society for Microbiology
%M DZNE-2025-00614
%P e0331424
%D 2025
%X 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.
%K Humans
%K rab5 GTP-Binding Proteins: metabolism
%K rab5 GTP-Binding Proteins: genetics
%K Virus Replication
%K SARS-CoV-2: physiology
%K SARS-CoV-2: genetics
%K Animals
%K COVID-19: virology
%K Host-Pathogen Interactions
%K Vero Cells
%K Chlorocebus aethiops
%K Viral Replication Compartments: metabolism
%K COP-I (Other)
%K COPB1 (Other)
%K NSP6 (Other)
%K RAB5 (Other)
%K SARS-CoV-2 (Other)
%K replication organelle (Other)
%K rab5 GTP-Binding Proteins (NLM Chemicals)
%K RAB5C protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40167317
%2 pmc:PMC12077180
%R 10.1128/mbio.03314-24
%U https://pub.dzne.de/record/278658