Repurposing the Antiplatelet Agent Ticlopidine to Counteract the Acute Phase of ER Stress Condition: An Opportunity for Fighting Coronavirus Infections and Cancer
Anna Tesei,
Michela Cortesi,
Martina Bedeschi,
Noemi Marino,
Giacomo Rossino,
Roberta Listro,
Daniela Rossi,
Pasquale Linciano,
Simona Collina
Affiliations
Anna Tesei
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
Michela Cortesi
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
Martina Bedeschi
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
Noemi Marino
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
Giacomo Rossino
Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
Roberta Listro
Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
Daniela Rossi
Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
Pasquale Linciano
Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
Simona Collina
Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
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. The promising results obtained suggest the potential use of ticlopidine to counteract ER stress induced by viral infections, such as COVID-19, and cancer.
