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

Virology

Department of Microbiology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, 930-0194, Japan; Department of Virology I, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan; Department of Virology, Toyama Institute of Health, Toyama, 939-0363, Japan. Electronic address:

Published: October 2023

AI Article Synopsis

  • The Lujo virus (LUJV) is a dangerous pathogen associated with hemorrhagic fever and there are currently no effective treatments available for it.
  • Researchers tested approved FDA drugs to find new antiviral options and discovered that certain cannabinoid receptor 1 (CB1) antagonists, like rimonabant, AM251, and AM281, can effectively inhibit LUJV entry into cells.
  • These CB1 antagonists not only blocked the virus's ability to fuse with cell membranes but also reduced the infection rate of LUJV in lab settings, highlighting their potential as candidates for future treatment developments.

Article 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 IC 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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2023.109867DOI Listing

Publication Analysis

Top Keywords

lujv
10
cannabinoid receptor
8
lujo virus
8
cb1 antagonists
8
rimonabant am251
8
am251 am281
8
fusion activity
8
activity lujv
8
inhibitors
4
inhibitors cannabinoid
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!