2. Academic Validation
  3. Wnt3a Facilitates SARS-CoV-2 Pseudovirus Entry into Cells

Wnt3a Facilitates SARS-CoV-2 Pseudovirus Entry into Cells

  • Int J Mol Sci. 2023 Dec 22;25(1):217. doi: 10.3390/ijms25010217.
Ivonne Melano 1,  Hui-Jye Chen 1,  Loveness Ngwira 2,  Pang-Hung Hsu 3 4 5,  Li-Lan Kuo 1,  Lloyd Noriega 1,  Wen-Chi Su 1 2 6 7
Affiliations

Affiliations

  • 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
  • 2 International Master's Program of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
  • 3 Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan.
  • 4 Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan.
  • 5 Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 6 Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
  • 7 Drug Development Center, China Medical University, Taichung 404, Taiwan.
PMID: 38203386 DOI: 10.3390/ijms25010217
Abstract

How ACE2 functions as the major host receptor of SARS-CoV-2 despite having low expression in the lungs is still unknown. To facilitate the development of therapeutic strategies against coronaviruses, gaining a deeper comprehension of the molecular mechanism of SARS-CoV-2 Infection is imperative. In our previous study, we identified several potential host factors of SARS-CoV-2 using an shRNA arrayed screen, one of which was Wnt3a. Here, we validated the significance of Wnt3a, a potent activator of the Wnt/β-catenin signaling pathway, for SARS-CoV-2 entry into cells by evaluating the effects of its knockdown and overexpression on SARS-CoV-2 pseudotyped virus entry. Further analysis revealed that SARS-CoV-2 pseudotyped virus Infection activates the canonical Wnt/β-catenin signaling pathway, which we found could subsequently stimulate ACE2 transcription. Collectively, our study identified Wnt3a as an important host factor that facilitates ACE2-mediated virus Infection. Insight into the virus entry mechanism is impactful as it will aid in developing novel therapeutic strategies against current and future coronavirus pandemics.

Keywords

ACE2; SARS-CoV-2; Wnt3a; canonical pathway; host factor; virus entry; β-catenin.

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