Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2
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 w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/10/3622 |
| _version_ | 1797567457938898944 |
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| author | Lucia Longhitano Daniele Tibullo Cesarina Giallongo Giacomo Lazzarino Nicola Tartaglia Sara Galimberti Giovanni Li Volti Giuseppe Alberto Palumbo Arcangelo Liso |
| author_facet | Lucia Longhitano Daniele Tibullo Cesarina Giallongo Giacomo Lazzarino Nicola Tartaglia Sara Galimberti Giovanni Li Volti Giuseppe Alberto Palumbo Arcangelo Liso |
| author_sort | Lucia Longhitano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:42:14Z |
| format | Article |
| id | doaj.art-d40696340e1648038cf071bffabd70f0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:42:14Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d40696340e1648038cf071bffabd70f02023-11-20T01:09:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110362210.3390/ijms21103622Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2Lucia Longhitano0Daniele Tibullo1Cesarina Giallongo2Giacomo Lazzarino3Nicola Tartaglia4Sara Galimberti5Giovanni Li Volti6Giuseppe Alberto Palumbo7Arcangelo Liso8Section of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalySection of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalySection of Haematology, Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia”, University of Catania, 95123 Catania, ItalyUniCamillus—Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, ItalySection of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, 56121 Pisa, ItalySection of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalySection of Haematology, Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia”, University of Catania, 95123 Catania, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, ItalyThe 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.https://www.mdpi.com/1422-0067/21/10/3622SARS-CoV-2proteasome inhibitorsendoplasmic stressUPR response |
| spellingShingle | Lucia Longhitano Daniele Tibullo Cesarina Giallongo Giacomo Lazzarino Nicola Tartaglia Sara Galimberti Giovanni Li Volti Giuseppe Alberto Palumbo Arcangelo Liso Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2 International Journal of Molecular Sciences SARS-CoV-2 proteasome inhibitors endoplasmic stress UPR response |
| title | Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2 |
| title_full | Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2 |
| title_fullStr | Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2 |
| title_full_unstemmed | Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2 |
| title_short | Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2 |
| title_sort | proteasome inhibitors as a possible therapy for sars cov 2 |
| topic | SARS-CoV-2 proteasome inhibitors endoplasmic stress UPR response |
| url | https://www.mdpi.com/1422-0067/21/10/3622 |
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