Inhibition of arenaviruses by combinations of orally available approved drugs
Autor: | Shawn Herring, Lisa Evans DeWald, Aidan O’Connor, Susan L. Fink, Mary F. Paine, Delaney Kirchmeier, Jessica M. Oda, Yuying Liang, Pamela J. Glass, Lisa M. Johansen, Tero Aittokallio, Stephen J. Polyak, Elizabeth A. Nelson, Aleksandr Ianevski, Jessica Wagoner, Gene G. Olinger, Qinfeng Huang, Judith M. White |
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Přispěvatelé: | Institute for Molecular Medicine Finland, Computational Systems Medicine, Helsinki Institute for Information Technology, Tero Aittokallio / Principal Investigator, Bioinformatics |
Rok vydání: | 2021 |
Předmět: |
MECHANISM
PHARMACOKINETICS viruses repurposing synergy Administration Oral medicine.disease_cause SynergyFinder2 Mice FUSION Chlorocebus aethiops Pharmacology (medical) 11832 Microbiology and virology 0303 health sciences biology virus diseases Lassa ANTIVIRAL ACTIVITY Drug Synergism Arenavirus 3. Good health EBOLA-VIRUS Infectious Diseases SINGLE INFLUENZA 317 Pharmacy Ebola Drug Therapy Combination Erratum filovirus medicine.drug_class broad-spectrum antiviral Lymphocytic choriomeningitis arbidol Antiviral Agents Proof of Concept Study Virus Cell Line Marburg 03 medical and health sciences Viral entry medicine Animals Arenaviridae Infections Humans Vero Cells 030304 developmental biology Pharmacology Ebola virus IDENTIFICATION SARS-CoV-2 030306 microbiology business.industry Junin biology.organism_classification medicine.disease Virology Lassa virus HEK293 Cells ARIPIPRAZOLE Pichinde Junin virus Antiviral drug business |
Zdroj: | Antimicrob Agents Chemother |
ISSN: | 0066-4804 |
Popis: | Correction: Volume65, Issue6 Article Numbere00653- 21 DOI10.1128/AAC.00653-21 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. |
Databáze: | OpenAIRE |
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