Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025)

Cyclophilins play a key role in the life cycle of coronaviruses. Alisporivir (Debio 025) is a nonimmunosuppressive analogue of cyclosporine with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective c...

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Veröffentlicht in:	Antimicrobial agents and chemotherapy 2020-06, Vol.64 (7), p.e00876-20
Hauptverfasser:	Softic, Laurent, Brillet, Rozenn, Berry, François, Ahnou, Nazim, Nevers, Quentin, Morin-Dewaele, Margot, Hamadat, Sabah, Bruscella, Patrice, Fourati, Slim, Pawlotsky, Jean-Michel, Ahmed-Belkacem, Abdelhakim
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antiviral Agents Antiviral Agents - pharmacology Betacoronavirus Betacoronavirus - drug effects Cell Line Chlorocebus aethiops Coronavirus Infections Coronavirus Infections - drug therapy COVID-19 Cyclophilins Cyclophilins - antagonists & inhibitors Cyclosporine Cyclosporine - pharmacology Humans Life Sciences Microbiology and Parasitology Pandemics Pneumonia, Viral Pneumonia, Viral - drug therapy SARS-CoV-2 Vero Cells Virology Virus Replication - drug effects
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Beschreibung
Zusammenfassung:	Cyclophilins play a key role in the life cycle of coronaviruses. Alisporivir (Debio 025) is a nonimmunosuppressive analogue of cyclosporine with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC ) of 0.46 ± 0.04 μM. Alisporivir inhibited a postentry step of the SARS-CoV-2 life cycle. These results justify rapidly conducting a proof-of-concept phase 2 trial with alisporivir in patients with SARS-CoV-2 infection.
ISSN:	0066-4804 1098-6596
DOI:	10.1128/AAC.00876-20