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

Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00876-20. doi: 10.1128/AAC.00876-20. Print 2020 Jun 23.

Abstract

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 (EC50) 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.

Keywords: SARS-CoV-2; alisporivir; antiviral; cyclophilin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Betacoronavirus / drug effects*
  • COVID-19
  • Cell Line
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy*
  • Cyclophilins / antagonists & inhibitors*
  • Cyclosporine / pharmacology*
  • Humans
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • SARS-CoV-2
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Cyclosporine
  • Cyclophilins
  • alisporivir