Journal
CELL DEATH & DISEASE
Volume 11, Issue 8, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-020-02842-x
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Funding
- Ligue contre le Cancer (equipe labellisee)
- Agence National de la Recherche (ANR) - Projets blancs
- ANR
- AMMICa US23/CNRS [UMS3655]
- Association pour la recherche sur le cancer (ARC)
- Association Le Cancer du Sein, Parlons-en!
- Canceropole Ile-de-France
- Chancelerie des universites de Paris (Legs Poix)
- Fondation pour la Recherche Medicale (FRM)
- European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR)
- Gustave Roussy Odyssea
- European Union Horizon 2020 Project Oncobiome
- Fondation Carrefour
- High-end Foreign Expert Program in China [GDW20171100085]
- Institut National du Cancer (INCa)
- Inserm (HTE)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx ImmunoOncology [ANR-18-IDEX-0001]
- RHU Torino Lumiere
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
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The current epidemic of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for the development of inhibitors of viral replication. Here, we performed a bioinformatic analysis of published and purported SARS-CoV-2 antivirals including imatinib mesylate that we found to suppress SARS-CoV-2 replication on Vero E6 cells and that, according to the published literature on other coronaviruses is likely to act on-target, as a tyrosine kinase inhibitor. We identified a cluster of SARS-CoV-2 antivirals with characteristics of lysosomotropic agents, meaning that they are lipophilic weak bases capable of penetrating into cells. These agents include cepharentine, chloroquine, chlorpromazine, clemastine, cloperastine, emetine, hydroxychloroquine, haloperidol, ML240, PB28, ponatinib, siramesine, and zotatifin (eFT226) all of which are likely to inhibit SARS-CoV-2 replication by non-specific (off-target) effects, meaning that they probably do not act on their 'official' pharmacological targets, but rather interfere with viral replication through non-specific effects on acidophilic organelles including autophagosomes, endosomes, and lysosomes. Imatinib mesylate did not fall into this cluster. In conclusion, we propose a tentative classification of SARS-CoV-2 antivirals into specific (on-target) versus non-specific (off-target) agents based on their physicochemical characteristics.
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