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Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19.
Blaess, Markus; Kaiser, Lars; Sommerfeld, Oliver; Csuk, René; Deigner, Hans-Peter.
  • Blaess M; Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Str. 17, D-78054 Villingen-Schwenningen, Germany.
  • Kaiser L; Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Str. 17, D-78054 Villingen-Schwenningen, Germany.
  • Sommerfeld O; Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, D-79104 Freiburg, Germany.
  • Csuk R; Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, D-07747 Jena, Germany.
  • Deigner HP; Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Int J Mol Sci ; 22(4)2021 Feb 11.
Article in English | MEDLINE | ID: covidwho-1079663
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Small Molecule Libraries / Drug Discovery / SARS-CoV-2 / COVID-19 Drug Treatment / Lysosomes Type of study: Prognostic study Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22041797

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Small Molecule Libraries / Drug Discovery / SARS-CoV-2 / COVID-19 Drug Treatment / Lysosomes Type of study: Prognostic study Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22041797