Inhibition of arenaviruses by combinations of orally available approved drugs

Shawn Herring, Jessica M. Oda, Jessica Wagoner, Delaney Kirchmeier, Aidan O'Connor, Elizabeth A. Nelson, Qinfeng Huang, Yuying Liang, Lisa Evans DeWald, Lisa M. Johansen, Pamela J. Glass, Gene G. Olinger, Aleksandr Ianevski, Tero Aittokallio, Mary F. Paine, Susan L. Fink, Judith M. White, Stephen J. Polyaka

Research output: Contribution to journalArticlepeer-review

Abstract

Neglected diseases caused by arenaviruses such as Lassa virus (LASV) and filoviruses like Ebola virus (EBOV) primarily afflict resource-limited countries, where antiviral drug development is often minimal. Previous studies have shown that many approved drugs developed for other clinical indications inhibit EBOV and LASV and that combinations of these drugs provide synergistic suppression of EBOV, often by blocking discrete steps in virus entry. We hypothesize that repurposing of combinations of orally administered approved drugs provides effective suppression of arenaviruses. In this report, we demonstrate that arbidol, an approved influenza antiviral previously shown to inhibit EBOV, LASV, and many other viruses, inhibits murine leukemia virus (MLV) reporter viruses pseudotyped with the fusion glycoproteins (GPs) of other arenaviruses (Junin virus [JUNV], lymphocytic choriomeningitis virus [LCMV], and Pichinde virus [PICV]). Arbidol and other approved drugs, including aripiprazole, amodiaquine, sertraline, and niclosamide, also inhibit infection of cells by infectious PICV, and arbidol, sertraline, and niclosamide inhibit infectious LASV. Combining arbidol with aripiprazole or sertraline results in the synergistic suppression of LASV and JUNV GP-bearing pseudoviruses. This proof-of-concept study shows that arenavirus infection in vitro can be synergistically inhibited by combinations of approved drugs. This approach may lead to a proactive strategy with which to prepare for and control known and new arenavirus outbreaks.

Original languageEnglish (US)
Article numbere01146-20
JournalAntimicrobial agents and chemotherapy
Volume65
Issue number4
DOIs
StatePublished - Apr 2021

Bibliographical note

Funding Information:
J.M.W. was partially supported by NIH grant AI114776; S.L.F. was partially supported by NIH grant AI119142. We gratefully acknowledge support from the Department of Laboratory Medicine and Pathology (University of Washington) and a Washington Research Foundation technology commercialization grant to S.J.P. S.J.P. and S.L.F. were also supported by a Building Bridges award from the Department of Laboratory Medicine and Pathology, University of Washington.

Publisher Copyright:
© 2021 American Society for Microbiology. All rights reserved.

Keywords

  • Arbidol
  • Arenavirus
  • Broad-spectrum antiviral
  • Ebola
  • Filovirus
  • Junin
  • Lassa
  • Marburg
  • Pichinde
  • Repurposing
  • SARS-CoV-2
  • Synergy
  • SynergyFinder2

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