Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2
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- Tia A. Tummino
- Department of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.
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- Veronica V. Rezelj
- Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.
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- Benoit Fischer
- Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.
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- Audrey Fischer
- Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.
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- Matthew J. O’Meara
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
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- Blandine Monel
- Institut Pasteur, Virus and Immunity Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.
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- Thomas Vallet
- Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.
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- Kris M. White
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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- Ziyang Zhang
- Quantitative Biosciences Institute (QBI), UCSF, San Francisco, CA, USA.
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- Assaf Alon
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
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- Heiko Schadt
- Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.
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- Henry R. O’Donnell
- Department of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.
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- Jiankun Lyu
- Department of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.
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- Romel Rosales
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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- Briana L. McGovern
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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- Raveen Rathnasinghe
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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- Sonia Jangra
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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- Michael Schotsaert
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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- Jean-René Galarneau
- Novartis Institutes for BioMedical Research, Preclinical Safety, Cambridge, MA, USA.
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- Nevan J. Krogan
- Quantitative Biosciences Institute (QBI), UCSF, San Francisco, CA, USA.
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- Laszlo Urban
- Novartis Institutes for BioMedical Research, Preclinical Safety, Cambridge, MA, USA.
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- Kevan M. Shokat
- Quantitative Biosciences Institute (QBI), UCSF, San Francisco, CA, USA.
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- Andrew C. Kruse
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
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- Adolfo García-Sastre
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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- Olivier Schwartz
- Institut Pasteur, Virus and Immunity Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.
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- Francesca Moretti
- Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.
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- Marco Vignuzzi
- Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, 75724 Paris, Cedex 15, France.
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- Francois Pognan
- Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.
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- Brian K. Shoichet
- Department of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.
説明
<jats:title>Screening for drugs that don’t work</jats:title> <jats:p> 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 <jats:italic>et al</jats:italic> . 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 </jats:p>
収録刊行物
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- Science
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Science 373 (6554), 541-547, 2021-07-30
American Association for the Advancement of Science (AAAS)