Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2 | Zendy

Tia A. Tummino | Zendy; Veronica V. Rezelj | Zendy; Benoit Fischer | Zendy; Audrey Fischer | Zendy; Matthew J. O’Meara | Zendy; Blandine Monel | Zendy; Thomas Vallet | Zendy; Kris M. White | Zendy; Ziyang Zhang | Zendy; Assaf Alon | Zendy; Heiko S. Schadt | Zendy; Henry O’Donnell | Zendy; Jiankun Lyu | Zendy; Romel Rosales | Zendy; Briana L. McGovern | Zendy; Raveen Rathnasinghe | Zendy; Sonia Jangra | Zendy; Michael Schotsaert | Zendy; JeanRene Galarneau | Zendy; Nevan J. Krogan | Zendy; László Urbán | Zendy; Kevan M. Shokat | Zendy; Andrew C. Kruse | Zendy; Adolfo Garcı́a-Sastre | Zendy; Olivier Schwartz | Zendy; Francesca Moretti | Zendy; Marco Vignuzzi | Zendy; François Pognan | Zendy; Brian K. Shoichet | Zendy

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Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2

Author(s) -

Tia A. Tummino,

Veronica V. Rezelj,

Benoit Fischer,

Audrey Fischer,

Matthew J. O’Meara,

Blandine Monel,

Thomas Vallet,

Kris M. White,

Ziyang Zhang,

Assaf Alon,

Heiko S. Schadt,

Henry O’Donnell,

Jiankun Lyu,

Romel Rosales,

Briana L. McGovern,

Raveen Rathnasinghe,

Sonia Jangra,

Michael Schotsaert,

JeanRene Galarneau,

Nevan J. Krogan,

László Urbán,

Kevan M. Shokat,

Andrew C. Kruse,

Adolfo Garcı́a-Sastre,

Olivier Schwartz,

Francesca Moretti,

Marco Vignuzzi,

François Pognan,

Brian K. Shoichet

Publication year - 2021

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.abi4708

Subject(s) - phospholipidosis , repurposing , drug repositioning , drug , pharmacology , hydroxychloroquine , drug discovery , drug development , covid-19 , medicine , biology , bioinformatics , disease , ecology , phospholipid , genetics , membrane , infectious disease (medical specialty)

Screening for drugs that don’t work In the battle against COVID-19, drugs discovered in repurposing screens are of particular interest because these could be rapidly implemented as treatments. However, Tumminoet 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

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