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Open AccessReview

Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2

1
Section of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
2
Section of Haematology, Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy
3
UniCamillus—Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy
4
Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy
5
Section of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, 56121 Pisa, Italy
*
Authors to whom correspondence should be addressed.
These authors equally contributed to this work as co-first.
These authors equally contributed to this work as co-last.
Int. J. Mol. Sci. 2020, 21(10), 3622; https://doi.org/10.3390/ijms21103622
Received: 29 April 2020 / Revised: 14 May 2020 / Accepted: 18 May 2020 / Published: 20 May 2020
(This article belongs to the Collection Stress, Immunity, and Tissue Microenvironment)
The COVID-19 global pandemic is caused by SARS-CoV-2, and represents an urgent medical and social issue. Unfortunately, there is still not a single proven effective drug available, and therefore, current therapeutic guidelines recommend supportive care including oxygen administration and treatment with antibiotics. Recently, patients have been also treated with off-label therapies which comprise antiretrovirals, anti-inflammatory compounds, antiparasitic agents and plasma from convalescent patients, all with controversial results. The ubiquitin–proteasome system (UPS) is important for the maintenance of cellular homeostasis, and plays a pivotal role in viral replication processes. In this review, we discuss several aspects of the UPS and the effects of its inhibition with particular regard to the life cycle of the coronaviruses (CoVs). In fact, proteasome inhibition by various chemical compounds, such as MG132, epoxomycin and bortezomib, may reduce the virus entry into the eucariotic cell, the synthesis of RNA, and the subsequent protein expression necessary for CoVs. Importantly, since UPS inhibitors reduce the cytokine storm associated with various inflammatory conditions, it is reasonable to assume that they might be repurposed for SARS-CoV-2, thus providing an additional tool to counteract both virus replication as well as its most deleterious consequences triggered by abnormal immunological response. View Full-Text
Keywords: SARS-CoV-2; proteasome inhibitors; endoplasmic stress; UPR response SARS-CoV-2; proteasome inhibitors; endoplasmic stress; UPR response
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MDPI and ACS Style

Longhitano, L.; Tibullo, D.; Giallongo, C.; Lazzarino, G.; Tartaglia, N.; Galimberti, S.; Li Volti, G.; Palumbo, G.A.; Liso, A. Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2. Int. J. Mol. Sci. 2020, 21, 3622.

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