tetano
Editor, Senior Moderator
mBio
. 2025 Apr 1:e0331424.
doi: 10.1128/mbio.03314-24. Online ahead of print. RAB5 is a host dependency factor for the generation of SARS-CoV-2 replication organelles
Yuexuan Chen[SUP] 1 [/SUP], Susanne Klute[SUP] 2 [/SUP], Konstantin Maria Johannes Sparrer[SUP] 2 3 [/SUP], Ruth Serra-Moreno[SUP] 1 [/SUP]
Affiliations
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[SUP]+[/SUP] 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: COP-I; COPB1; NSP6; RAB5; SARS-CoV-2; replication organelle.
. 2025 Apr 1:e0331424.
doi: 10.1128/mbio.03314-24. Online ahead of print. RAB5 is a host dependency factor for the generation of SARS-CoV-2 replication organelles
Yuexuan Chen[SUP] 1 [/SUP], Susanne Klute[SUP] 2 [/SUP], Konstantin Maria Johannes Sparrer[SUP] 2 3 [/SUP], Ruth Serra-Moreno[SUP] 1 [/SUP]
Affiliations
- PMID: 40167317
- DOI: 10.1128/mbio.03314-24
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[SUP]+[/SUP] 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: COP-I; COPB1; NSP6; RAB5; SARS-CoV-2; replication organelle.