Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Helena Obernolte¹  Katherina Sewald¹  Valeria Roll²  Jochen Bodem²  Sofie Fähr²  Viktoria Diesendorf²  Nina Geiger² 

[1] Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Hannover, Germany;Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany;

关键词: SARS-CoV-2;    phospholipidosis;    Vero E6;    PCLS;    Calu-3;    antivirals;    Tamoxifen;    cell line-specificity;   

DOI  :  10.3389/fcimb.2023.1100028

 received in 2022-11-16, accepted in 2023-07-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

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 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.

【 授权许可】

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Copyright © 2023 Diesendorf, Roll, Geiger, Fähr, Obernolte, Sewald and Bodem