Identifications of novel host cell factors that interact with the receptor-binding domain of the SARS-CoV-2 spike protein

Xiao Tang, Yang Liu, Jinhui Wang, Teng Long, Bobo Wing Yee Mok, Yan Huang, Ziqing Peng, Qinyu Jia, Chengxi Liu, Pui Kin So, Sirius Pui-Kam Tse, Cheuk Hei NG, Shiyi Liu, Fei Sun, Shaojun Tang, Zhong Ping Yao, Honglin Chen, Yusong Guo

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

Abstract

SARS-CoV-2 entry into host cells is facilitated by the interaction between the receptor-binding domain of its spike protein (CoV2-RBD) and host cell receptor, ACE2, promoting viral membrane fusion. The virus also uses endocytic pathways for entry, but the mediating host factors remain largely unknown. It is also unknown whether mutations in the RBD of SARS-CoV-2 variants promote interactions with additional host factors to promote viral entry. Here, we used the GST pull-down approach to identify novel surface-located host factors that bind to CoV2-RBD. One of these factors, SH3BP4, regulates internalization of CoV2-RBD in an ACE2-independent but integrin- and clathrin-dependent manner and mediates SARS-CoV-2 pseudovirus entry, suggesting that SH3BP4 promotes viral entry via the endocytic route. Many of the identified factors, including SH3BP4, ADAM9, and TMEM2, show stronger affinity to CoV2-RBD than to RBD of the less infective SARS-CoV, suggesting SARS-CoV-2–specific utilization. We also found factors preferentially binding to the RBD of the SARS-CoV-2 Delta variant, potentially enhancing its entry. These data identify the repertoire of host cell surface factors that function in the events leading to the entry of SARS-CoV-2.

Original languageEnglish
Article number107390
JournalJournal of Biological Chemistry
Volume300
Issue number6
DOIs
Publication statusPublished - Jun 2024

Keywords

  • ACE2
  • integrin
  • SARS-CoV-2
  • SH3BP4
  • the receptor binding domain of spike
  • viral entry

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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