PMID- 33468464 OWN - NLM STAT- MEDLINE DCOM- 20210401 LR - 20240403 IS - 1098-6596 (Electronic) IS - 0066-4804 (Print) IS - 0066-4804 (Linking) VI - 65 IP - 4 DP - 2021 Mar 18 TI - Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs. LID - 10.1128/AAC.01146-20 [doi] LID - e01146-20 AB - 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. CI - Copyright (c) 2021 Herring et al. FAU - Herring, Shawn AU - Herring S AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA. FAU - Oda, Jessica M AU - Oda JM AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA. FAU - Wagoner, Jessica AU - Wagoner J AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA. FAU - Kirchmeier, Delaney AU - Kirchmeier D AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA. FAU - O'Connor, Aidan AU - O'Connor A AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA. FAU - Nelson, Elizabeth A AU - Nelson EA AD - Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA. FAU - Huang, Qinfeng AU - Huang Q AD - Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, Minnesota, USA. FAU - Liang, Yuying AU - Liang Y AD - Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, Minnesota, USA. FAU - DeWald, Lisa Evans AU - DeWald LE AD - Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA. FAU - Johansen, Lisa M AU - Johansen LM AD - Horizon Discovery, Cambridge, Massachusetts, USA. FAU - Glass, Pamela J AU - Glass PJ AD - Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA. FAU - Olinger, Gene G AU - Olinger GG AD - MRIGlobal, Gaithersburg, Maryland, USA. FAU - Ianevski, Aleksandr AU - Ianevski A AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. FAU - Aittokallio, Tero AU - Aittokallio T AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. AD - Oslo Centre for Biostatistics and Epidemiology (OCBE), University of Oslo, Oslo, Norway. AD - Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. FAU - Paine, Mary F AU - Paine MF AUID- ORCID: 0000-0002-3331-1839 AD - Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA. FAU - Fink, Susan L AU - Fink SL AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA. FAU - White, Judith M AU - White JM AUID- ORCID: 0000-0002-0532-996X AD - Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA. AD - Department of Microbiology, University of Virginia, Charlottesville, Virginia, USA. FAU - Polyak, Stephen J AU - Polyak SJ AUID- ORCID: 0000-0001-7475-9827 AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA polyak@uw.edu. AD - Department of Global Health, University of Washington, Seattle, Washington, USA. AD - Department of Microbiology, University of Washington, Seattle, Washington, USA. LA - eng GR - K08 AI119142/AI/NIAID NIH HHS/United States GR - R01 AI114776/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210318 PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Antiviral Agents) SB - IM EIN - Antimicrob Agents Chemother. 2021 May 18;65(6):. PMID: 34006613 MH - Administration, Oral MH - Animals MH - Antiviral Agents/*therapeutic use MH - Arenaviridae Infections/*drug therapy/virology MH - Arenavirus/*drug effects MH - Cell Line MH - Chlorocebus aethiops MH - Drug Synergism MH - Drug Therapy, Combination/methods MH - HEK293 Cells MH - Humans MH - Mice MH - Proof of Concept Study MH - Vero Cells PMC - PMC8097473 OTO - NOTNLM OT - Ebola OT - Junin OT - Lassa OT - Marburg OT - Pichinde OT - SARS-CoV-2 OT - SynergyFinder2 OT - arbidol OT - arenavirus OT - broad-spectrum antiviral OT - filovirus OT - repurposing OT - synergy EDAT- 2021/01/21 06:00 MHDA- 2021/04/02 06:00 PMCR- 2021/03/18 CRDT- 2021/01/20 05:42 PHST- 2020/06/04 00:00 [received] PHST- 2020/12/24 00:00 [accepted] PHST- 2021/01/21 06:00 [pubmed] PHST- 2021/04/02 06:00 [medline] PHST- 2021/01/20 05:42 [entrez] PHST- 2021/03/18 00:00 [pmc-release] AID - AAC.01146-20 [pii] AID - 01146-20 [pii] AID - 10.1128/AAC.01146-20 [doi] PST - epublish SO - Antimicrob Agents Chemother. 2021 Mar 18;65(4):e01146-20. doi: 10.1128/AAC.01146-20. Print 2021 Mar 18.