PMID- 37637460
OWN - NLM
STAT- MEDLINE
DCOM- 20230829
LR  - 20230831
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 13
DP  - 2023
TI  - Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 
      - inhibition of SARS-CoV-2 is cell line-specific.
PG  - 1100028
LID - 10.3389/fcimb.2023.1100028 [doi]
LID - 1100028
AB  - 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.
CI  - Copyright (c) 2023 Diesendorf, Roll, Geiger, Fahr, Obernolte, Sewald and Bodem.
FAU - Diesendorf, Viktoria
AU  - Diesendorf V
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Roll, Valeria
AU  - Roll V
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Geiger, Nina
AU  - Geiger N
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Fahr, Sofie
AU  - Fahr S
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Obernolte, Helena
AU  - Obernolte H
AD  - 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.
FAU - Sewald, Katherina
AU  - Sewald K
AD  - 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.
FAU - Bodem, Jochen
AU  - Bodem J
AD  - Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230811
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - O6W7VEW6KS (Tilorone)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 0 (Antiviral Agents)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - Humans
MH  - *Tilorone
MH  - *COVID-19
MH  - Fluoxetine
MH  - SARS-CoV-2
MH  - Antiviral Agents/pharmacology
MH  - Cell Line
MH  - Chloroquine
PMC - PMC10450944
OTO - NOTNLM
OT  - Calu-3
OT  - PCLS
OT  - SARS-CoV-2
OT  - Tamoxifen
OT  - Vero E6
OT  - antivirals
OT  - cell line-specificity
OT  - phospholipidosis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/08/28 06:42
MHDA- 2023/08/29 12:44
PMCR- 2023/08/11
CRDT- 2023/08/28 04:49
PHST- 2022/11/16 00:00 [received]
PHST- 2023/07/25 00:00 [accepted]
PHST- 2023/08/29 12:44 [medline]
PHST- 2023/08/28 06:42 [pubmed]
PHST- 2023/08/28 04:49 [entrez]
PHST- 2023/08/11 00:00 [pmc-release]
AID - 10.3389/fcimb.2023.1100028 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2023 Aug 11;13:1100028. doi: 
      10.3389/fcimb.2023.1100028. eCollection 2023.