Characterization of new host cell surface protein affecting SARS-CoV-2 entry

ContributorsBesomi, Alicia
Number of pages59
Master program titleBiologie générale
Imprimatur date2023-01-25

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first surfaced in the end of 2019. It is a highly transmissible and dangerous coronavirus. It has brought upon us a pandemic of acute respiratory illness known as COVID-19, which poses a risk to both human health and public safety (1). This virus has a spike protein on its surface, which is the key to its entry into host cells. This spike protein has two subunits: S1 and S2. It also has two different protease cleavage sites, one in between the two subunits called the S1/S2 cleavage site which is cleaved by furin (2). And the second one in the S2 subunit called S2’, is cleaved by transmembrane serine protease-2 (TMPRSS2) on the cell surface or cathepsin L in the endosome (3). The spike protein binds to angiotensin-converting enzyme 2 (ACE2) receptor post furin cleavage to enter the cells (4). Researchers have shown that cells devoid of this receptor were also susceptible to SARS-CoV-2 infection (5,6). We wanted to find new host cell surface proteins that are involved in SARS-CoV-2 entry. The environment of the SARS-CoV-2 virion during entry is still not fully understood, hence the importance of the study. Based on a short list of target proteins identified with a cell surface proximity ligation assay, we used a CRISPR-Cas9 knockout approach, and identified six proteins: AXL, PROM1, LY75, F3, ERBB2 and ICAM1 as potential inhibitors of SARS-CoV-2 entry. Moreover, by performing genetic overexpression of these proteins, we observed that ERBB2 overexpression led to a reduction in viral entry, making it more likely that this protein will function an inhibitor of entry. We detected a decrease in the expression of the S2 subunit during the co-transfection of AXL, PROM1 and LY75 with the spike protein. Therefore, these proteins might be potential inhibitors of the furin cleavage process. We can conclude that ERBB2 could be a potential inhibitor of SARS-CoV-2 entry and that AXL, PROM1 and LY75 might be involved in the furin cleavage of spike, but we still need to investigate the underlying mechanisms.

Citation (ISO format)
BESOMI, Alicia. Characterization of new host cell surface protein affecting SARS-CoV-2 entry. 2023.
Main files (1)
Master thesis
  • PID : unige:166765

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