Ursodeoxycholic Acid Attenuates B Cell Susceptibility to SARS-CoV-2 Spike Protein by Interfering Its Binding to ACE2

So-Jeong Park; Eun-Yi Moon

So-Jeong Park, Eun-Yi Moon

Biomolecules & Therapeutics, doi:10.4062/biomolther.2025.149

B cells are essential for the defense against various infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) causing coronavirus disease 2019 . COVID-19 is caused by interaction of the spike protein (SP) with the receptor-binding domain (RBD) and its receptor, angiotensin converting enzyme 2 (ACE2). Bisphenol A (BPA), a plasticizer and endocrine-disrupting chemical, can enter the human body through several exposure routes. Previously, we reported human B cell death by BPA treatment via autophagy induction. Here, we investigated whether the exposure to BPA affects B cell susceptibility to SP of COVID-19 and how to interfere the interaction of SP and ACE2. We observed an increase in ACE2 gene expression in human B cells by BPA treatment and more SP binding in BPA-treated B cells. Our data also showed more B cell death accompanying increased autophagic puncta count and lysosomal intracellular activity by co-treatment with BPA and SP compared to those in BPA treatment alone. Ursodeoxycholic acid (UDCA) reduced SP binding in B cells in BPA-exposed B cells. UDCA treatment also inhibited B cell death and lysosomal enzyme activity which were enhanced by co-treatment of BPA and SP. Taken together, results demonstrate that BPA-exposed B cells are more susceptible to COVID-19. It also suggests that UDCA could be protective to SP-responding B cells exposed to BPA.

CONFLICT OF INTEREST The authors declare no competing financial and non-financial interests. AUTHOR CONTRIBUTIONS SJP settled down and conducted the experiments, and wrote primary manuscript. EYM planed main idea of the study, analyzed the results, corrected the manuscript, and supported SJP to provide reagents, materials and analysis tools. All authors reviewed the manuscript.

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