Inhibitors of cannabinoid receptor 1 suppress the cellular entry of Lujo virus

Miyuki Kimura, Risa Matsuoka, Satoshi Taniguchi, Junki Maruyama, Slobodan Paessler, Saori Oka, Atsushi Yamashita, Takasuke Fukuhara, Yoshiharu Matsuura, Hideki Tani

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Lujo virus (LUJV), which belongs to Mammarenavirus, family Arenaviridae, has emerged as a pathogen causing severe hemorrhagic fever with high mortality. Currently, there are no effective treatments for arenaviruses, including LUJV. Here, we screened chemical compound libraries of Food and Drug Administration (FDA)-approved drugs and G protein-coupled receptor-associated drugs to identify effective antivirals against LUJV targeting cell entry using a vesicular stomatitis virus-based pseudotyped virus bearing the LUJV envelope glycoprotein (GP). Cannabinoid receptor 1 (CB1) antagonists, such as rimonabant, AM251 and AM281, have been identified as robust inhibitors of LUJV entry. The IC50 of rimonabant was 0.26 and 0.53 μM in Vero and Huh7 cells, respectively. Analysis of the cell fusion activity of the LUJV GP in the presence of CB1 inhibitors revealed that these inhibitors suppressed the fusion activity of the LUJV GP. Moreover, rimonabant, AM251 and AM281 reduced the infectivity of authentic LUJV in vitro, suggesting that the antiviral activity of CB1 antagonists against LUJV is mediated, at least in part, by inhibition of the viral entry, especially, membrane fusion. These findings suggest promising candidates for developing new therapies against LUJV infections.

Original languageEnglish (US)
Article number109867
JournalVirology
Volume587
DOIs
StatePublished - Oct 2023

Keywords

  • CB1 inhibitors
  • Cell fusion
  • Lujo virus
  • Pseudotyped virus

ASJC Scopus subject areas

  • Virology

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