Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19
Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1797 |
| _version_ | 1797396877064273920 |
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| author | Markus Blaess Lars Kaiser Oliver Sommerfeld René Csuk Hans-Peter Deigner |
| author_facet | Markus Blaess Lars Kaiser Oliver Sommerfeld René Csuk Hans-Peter Deigner |
| author_sort | Markus Blaess |
| collection | DOAJ |
| description | Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic. |
| first_indexed | 2024-03-09T00:57:49Z |
| format | Article |
| id | doaj.art-94f5d26d01ec41a7abfa3092817e4ec9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:57:49Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-94f5d26d01ec41a7abfa3092817e4ec92023-12-11T16:46:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224179710.3390/ijms22041797Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19Markus Blaess0Lars Kaiser1Oliver Sommerfeld2René Csuk3Hans-Peter Deigner4Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Str. 17, D-78054 Villingen-Schwenningen, GermanyInstitute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Str. 17, D-78054 Villingen-Schwenningen, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, D-07747 Jena, GermanyOrganic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), GermanyInstitute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Str. 17, D-78054 Villingen-Schwenningen, GermanyLysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.https://www.mdpi.com/1422-0067/22/4/1797SARS-CoV-2COVID-19lysosomotropismmetabolitescytokine stormviral host cell entry |
| spellingShingle | Markus Blaess Lars Kaiser Oliver Sommerfeld René Csuk Hans-Peter Deigner Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19 International Journal of Molecular Sciences SARS-CoV-2 COVID-19 lysosomotropism metabolites cytokine storm viral host cell entry |
| title | Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19 |
| title_full | Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19 |
| title_fullStr | Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19 |
| title_full_unstemmed | Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19 |
| title_short | Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19 |
| title_sort | drugs metabolites and lung accumulating small lysosomotropic molecules multiple targeting impedes sars cov 2 infection and progress to covid 19 |
| topic | SARS-CoV-2 COVID-19 lysosomotropism metabolites cytokine storm viral host cell entry |
| url | https://www.mdpi.com/1422-0067/22/4/1797 |
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