Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2
Abstract
In the battle against COVID-19, drugs discovered in repurposing screens are of particular interest because these could be rapidly implemented as treatments. However, Tummino et al . deliver a cautionary tale, finding that many leads from such screens have an antiviral effect in cells through phospholipidosis, a phospholipid storage disorder that can be induced by cationic amphiphilic drugs (see the Perspective by Edwards and Hartung). There is a strong correlation between drug-induced phospholipidosis and inhibition of severe acute respiratory syndrome coronavirus 2 replication in cells. Unfortunately, drugs that have an antiviral effect in cells through phospholipidosis are unlikely to be effective in vivo. Screening out such drugs may allow a focus on drugs with better clinical potential. —VV
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 30, 2021
- Source ID
- 10.1126/science.abi4708
Entities
People
- Adolfo García-Sastre
- Andrew C Kruse
- Assaf Alon
- Audrey Fischer
- Benoit Fischer
- Blandine Monel
- Brian K. Shoichet
- Briana L. McGovern
- Francesca Moretti
- Francois Pognan
- Heiko Schadt
- Henry O’Donnell
- Jean-rené Galarneau
- Jiankun Lyu
- Kevan M. Shokat
- Kris M White
- Laszlo Urban
- Marco Vignuzzi
- Matthew J O'Meara
- Michael Schotsaert
- Nevan Krogan
- Olivier Schwartz
- Raveen Rathnasinghe
- Romel Rosales
- Sonia Jangra
- Thomas Vallet
- Tia A Tummino
- Veronica Rezelj
- Ziyang Zhang
Organizations
- ASCRS Research Foundation
- Damon Runyon Cancer Research Foundation
- Defense Advanced Research Projects Agency
- George Mason University
- Harvard Medical School
- Howard Hughes Medical Institute
- Icahn School of Medicine at Mount Sinai
- National Institute of Allergy and Infectious Diseases
- National Institute of General Medical Sciences
- National Institutes of Health
- Novartis Institutes for BioMedical Research
- Open Philanthropy Project
- Pasteur Institute
- University of California, San Francisco
- University of Michigan