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001     278658
005     20250601001327.0
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037 _ _ |a DZNE-2025-00614
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Chen, Yuexuan
|b 0
245 _ _ |a RAB5 is a host dependency factor for the generation of SARS-CoV-2 replication organelles.
260 _ _ |a Washington, DC
|c 2025
|b American Society for Microbiology
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520 _ _ |a 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.
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650 _ 7 |a COP-I
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650 _ 7 |a COPB1
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650 _ 7 |a NSP6
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650 _ 7 |a RAB5
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650 _ 7 |a SARS-CoV-2
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650 _ 7 |a replication organelle
|2 Other
650 _ 7 |a rab5 GTP-Binding Proteins
|0 EC 3.6.5.2
|2 NLM Chemicals
650 _ 7 |a RAB5C protein, human
|0 EC 3.6.1.-
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a rab5 GTP-Binding Proteins: metabolism
|2 MeSH
650 _ 2 |a rab5 GTP-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a Virus Replication
|2 MeSH
650 _ 2 |a SARS-CoV-2: physiology
|2 MeSH
650 _ 2 |a SARS-CoV-2: genetics
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a COVID-19: virology
|2 MeSH
650 _ 2 |a Host-Pathogen Interactions
|2 MeSH
650 _ 2 |a Vero Cells
|2 MeSH
650 _ 2 |a Chlorocebus aethiops
|2 MeSH
650 _ 2 |a Viral Replication Compartments: metabolism
|2 MeSH
700 1 _ |a Klute, Susanne
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700 1 _ |a Sparrer, Konstantin Maria Johannes
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700 1 _ |a Serra-Moreno, Ruth
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773 _ _ |a 10.1128/mbio.03314-24
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