Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection.

Abstract

The severity of the SARS-CoV-2 pandemic and the recurring (re)emergence of viruses prompted the development of new therapeutic approaches that target viral and host factors crucial for viral infection. Among them, host peptidases cathepsins B and L have been described as essential enzymes during SARS-CoV-2 entry. In this study, we evaluated the effect of potent selective cathepsin inhibitors as antiviral agents. We demonstrated that selective cathepsin B inhibitors, such as the antimicrobial agent nitroxoline and its derivatives, impair SARS-CoV-2 infection in vitro. Antiviral activity observed at early stage of virus entry was cell-type dependent and correlated well with the intracellular content and enzymatic function of cathepsins B or L. Furthermore, tested inhibitors were effective against the ancestral SARS-CoV-2 D614 as well as against the more recent BA.1_4 (Omicron). Taken together, our results highlight the important role of host cysteine cathepsin B in SARS-CoV-2 virus entry and show that cathepsin-specific inhibitors, such as nitroxoline and its derivatives, could be used to treat COVID-19. Finally, these results also suggest that nitroxoline has potential to be further explored as repurposed drug in antiviral therapy.

• Authors: Rafaela Milan Bonotto, Ana Mitrović, Izidor Sosič, Pamela Martínez-Orellana, Federica Dattola, Stanislav Gobec, Janko Kos, Alessandro Marcello
• Journal: Antiviral research (Antiviral Res) Vol. 216 Pg. 105655 (08 2023) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 37355023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Cathepsin B
• nitroxoline
• Antiviral Agents

Topics

• Humans
• COVID-19
• Cathepsin B (pharmacology)
• SARS-CoV-2
• Antiviral Agents (pharmacology)
• Virus Internalization