Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific
Please always quote using this URN: urn:nbn:de:bvb:20-opus-326202
- Recently, Tummino et al. reported that 34 compounds, including Chloroquine and Fluoxetine, inhibit SARS-CoV-2 replication by inducing phospholipidosis, although Chloroquine failed to suppress viral replication in Calu-3 cells and patients. In contrast, Fluoxetine represses viral replication in human precision-cut lung slices (PCLS) and Calu-3 cells. Thus, it is unlikely that these compounds have similar mechanisms of action. Here, we analysed a subset of these compounds in the viral replication and phospholipidosis assays using the Calu-3 cellsRecently, Tummino et al. reported that 34 compounds, including Chloroquine and Fluoxetine, inhibit SARS-CoV-2 replication by inducing phospholipidosis, although Chloroquine failed to suppress viral replication in Calu-3 cells and patients. In contrast, Fluoxetine represses viral replication in human precision-cut lung slices (PCLS) and Calu-3 cells. Thus, it is unlikely that these compounds have similar mechanisms of action. Here, we analysed a subset of these compounds in the viral replication and phospholipidosis assays using the Calu-3 cells and PCLS as the patient-near system. Trimipramine and Chloroquine induced phospholipidosis but failed to inhibit SARS-CoV-2 replication in Calu-3 cells, which contradicts the reported findings and the proposed mechanism. Fluoxetine, only slightly induced phospholipidosis in Calu-3 cells but reduced viral replication by 2.7 orders of magnitude. Tilorone suppressed viral replication by 1.9 orders of magnitude in Calu-3 cells without causing phospholipidosis. Thus, induction of phospholipidosis is not correlated with the inhibition of SARS-CoV-2, and the compounds act via other mechanisms. However, we show that compounds, such as Amiodarone, Tamoxifen and Tilorone, with antiviral activity on Calu-3 cells, also inhibited viral replication in human PCLS. Our results indicate that antiviral assays against SARS-CoV-2 are cell-line specific. Data from Vero E6 can lead to non-transferable results, underlining the importance of an appropriate cell system for analysing antiviral compounds against SARS-CoV-2. We observed a correlation between the active compounds in Calu-3 cells and PCLS.…
Author: | Viktoria Diesendorf, Valeria Roll, Nina Geiger, Sofie Fähr, Helena Obernolte, Katherina Sewald, Jochen Bodem |
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URN: | urn:nbn:de:bvb:20-opus-326202 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Language: | English |
Parent Title (English): | Frontiers in Cellular and Infection Microbiology |
ISSN: | 2235-2988 |
Year of Completion: | 2023 |
Volume: | 13 |
Article Number: | 1100028 |
Source: | Frontiers in Cellular and Infection Microbiology (2023) 13:1100028. https://doi.org/10.3389/fcimb.2023.1100028 |
DOI: | https://doi.org/10.3389/fcimb.2023.1100028 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | Calu-3; PCLS; SARS-CoV-2; Tamoxifen; Vero E6; antivirals; cell line-specificity; phospholipidosis |
Release Date: | 2024/05/08 |
Date of first Publication: | 2023/08/11 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |