Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2.
Science
; 373(6554): 541-547, 2021 07 30.
Article
in English
| MEDLINE | ID: covidwho-1334531
ABSTRACT
Repurposing drugs as treatments for COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drawn much attention. Beginning with sigma receptor ligands and expanding to other drugs from screening in the field, we became concerned that phospholipidosis was a shared mechanism underlying the antiviral activity of many repurposed drugs. For all of the 23 cationic amphiphilic drugs we tested, including hydroxychloroquine, azithromycin, amiodarone, and four others already in clinical trials, phospholipidosis was monotonically correlated with antiviral efficacy. Conversely, drugs active against the same targets that did not induce phospholipidosis were not antiviral. Phospholipidosis depends on the physicochemical properties of drugs and does not reflect specific target-based activities-rather, it may be considered a toxic confound in early drug discovery. Early detection of phospholipidosis could eliminate these artifacts, enabling a focus on molecules with therapeutic potential.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Phospholipids
/
Drug Repositioning
/
SARS-CoV-2
/
COVID-19 Drug Treatment
/
Lipidoses
Type of study:
Diagnostic study
/
Prognostic study
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Science
Year:
2021
Document Type:
Article
Affiliation country:
Science.abi4708
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