2. Academic Validation
  3. UBXN7 facilitates SARS-CoV-2 replication via inhibiting the K48-linked ubiquitination of viral N protein

UBXN7 facilitates SARS-CoV-2 replication via inhibiting the K48-linked ubiquitination of viral N protein

  • PLoS Pathog. 2025 Oct 14;21(10):e1013593. doi: 10.1371/journal.ppat.1013593.
Tian Xia 1,  Min Luo 2,  Yuncheng Wang 1,  Yaping Qin 3,  Xiaoning Li 1,  Shuying Chen 1,  Junqi Xiang 1,  Shanrong Yang 1,  Yaokai Wang 1,  Jing Zhu 1,  Bo Yang 1,  Li Lin 4,  Jiajun Yan 1,  Yunxiao Dou 1,  Jian Shang 3,  Na Zang 4,  Yong Lin 5,  Xiaohong Yao 2,  Yushun Wan 1 4
Affiliations

Affiliations

  • 1 College of Basic Medicine, Chongqing Medical University, China.
  • 2 Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • 3 Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
  • 4 Department of Respiratory Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China.
  • 5 Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, China.
PMID: 41086194 DOI: 10.1371/journal.ppat.1013593
Abstract

Host factor-mediated post-translational modification of coronavirus proteins has been demonstrated as an important strategy for regulating viral proliferation. Identification of key host genes involved in this process may provide potential therapeutic targets. In this study, we used the complementary reverse genetic system to determine that UBXN7 promotes SARS-CoV-2 viral double-stranded RNA (dsRNA) production and also promotes the replication of Other human coronaviruses. However, UBXN7 does not affect the replication of VSV and RSV, suggesting that it may be a potential pan human coronaviral Anti-infection target. Our results revealed that UBXN7 did not affect the viral invasion of cells, but instead hijacked viral genome assembly by interacting with SARS-CoV-2 N protein via its UBX domain. Further data indicated that UBXN7 inhibits K48-linked ubiquitination and proteasomal degradation of SARS-CoV-2 N protein, leading to N protein accumulation. Moreover, K257 of N protein was identified as specific target site of UBXN7 which are critical for viral replication. These findings reveal a novel relationship between host gene-mediated protein ubiquitylation and viral genome assembly, providing new strategies for potential pan-coronavirus drug design.

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