Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs

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Herring , S , Oda , J M , Wagoner , J , Kirchmeier , D , O'Connor , A , Nelson , E A , Huang , Q , Liang , Y , DeWald , L E , Johansen , L M , Glass , P J , Olinger , G G , Ianevski , A , Aittokallio , T , Paine , M F , Fink , S L , White , J M & Polyak , S J 2021 , ' Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs ' , Antimicrobial Agents and Chemotherapy , vol. 65 , no. 4 , e01146-20 . https://doi.org/10.1128/AAC.01146-20

Title: Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs
Author: Herring, Shawn; Oda, Jessica M.; Wagoner, Jessica; Kirchmeier, Delaney; O'Connor, Aidan; Nelson, Elizabeth A.; Huang, Qinfeng; Liang, Yuying; DeWald, Lisa Evans; Johansen, Lisa M.; Glass, Pamela J.; Olinger, Gene G.; Ianevski, Aleksandr; Aittokallio, Tero; Paine, Mary F.; Fink, Susan L.; White, Judith M.; Polyak, Stephen J.
Contributor organization: Institute for Molecular Medicine Finland
Computational Systems Medicine
Helsinki Institute for Information Technology
Tero Aittokallio / Principal Investigator
Bioinformatics
Date: 2021-04
Language: eng
Number of pages: 17
Belongs to series: Antimicrobial Agents and Chemotherapy
ISSN: 0066-4804
DOI: https://doi.org/10.1128/AAC.01146-20
URI: http://hdl.handle.net/10138/332459
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 (PICA). 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.
Description: Correction: Volume65, Issue6 Article Numbere00653- 21 DOI10.1128/AAC.00653-21
Subject: arenavirus
filovirus
Lassa
Junin
Pichinde
Ebola
Marburg
arbidol
repurposing
broad-spectrum antiviral
SARS-CoV-2
synergy
SynergyFinder2
EBOLA-VIRUS
ANTIVIRAL ACTIVITY
ARBIDOL
PHARMACOKINETICS
FUSION
IDENTIFICATION
ARIPIPRAZOLE
INFLUENZA
MECHANISM
SINGLE
11832 Microbiology and virology
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: acceptedVersion


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