Perspective on Antiplatelet AgentTiclopidine for Acute ER Stress

Anna Tesei

Different pathological conditions, including viral infections and cancer, can have a
massive impact on the endoplasmic reticulum (ER), causing severe damage to the cell
and exacerbating the disease. In particular, coronavirus infections, including SARS
coronavirus-2 (SARS-CoV-2), responsible for COVID-19, cause ER stress as a consequence
of the enormous amounts of viral glycoproteins synthesized, the perturbation of ER
homeostasis and the modification of ER membranes. Therefore, ER has a central role in the
viral life cycle, thus representing one of the Achilles’ heels on which to focus therapeutic
intervention. On the other hand, prolonged ER stress has been demonstrated to promote
many pro-tumoral attributes in cancer cells, having a key role in tumor growth, metastasis
and response to therapies. In this report, adopting a repurposing approach of approved
drugs, we identified the antiplatelet agent ticlopidine as an interferent of the unfolded
protein response (UPR) via sigma receptors (SRs) modulation.