Screening and Identification of Lujo Virus Inhibitors Using a Recombinant Reporter Virus Platform

Viruses. 2021 Jun 28;13(7):1255. doi: 10.3390/v13071255.

Abstract

Lujo virus (LUJV), a highly pathogenic arenavirus, was first identified in 2008 in Zambia. To aid the identification of effective therapeutics for LUJV, we developed a recombinant reporter virus system, confirming reporter LUJV comparability with wild-type virus and its utility in high-throughput antiviral screening assays. Using this system, we evaluated compounds with known and unknown efficacy against related arenaviruses, with the aim of identifying LUJV-specific and potential new pan-arenavirus antivirals. We identified six compounds demonstrating robust anti-LUJV activity, including several compounds with previously reported activity against other arenaviruses. These data provide critical evidence for developing broad-spectrum antivirals against high-consequence arenaviruses.

Keywords: Lujo virus; antiviral screen; arenavirus; emerging viruses; reporter virus; reverse genetics; therapeutic; viral hemorrhagic fever.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Arenaviridae Infections / drug therapy
  • Arenaviridae Infections / virology
  • Arenavirus / drug effects*
  • Arenavirus / physiology
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Genome, Viral
  • Green Fluorescent Proteins / genetics
  • Humans
  • Lujo virus / drug effects*
  • Lujo virus / genetics
  • Lujo virus / physiology
  • Microbial Sensitivity Tests
  • Recombinant Proteins
  • Vero Cells
  • Virus Internalization / drug effects

Substances

  • Antiviral Agents
  • Recombinant Proteins
  • Green Fluorescent Proteins