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
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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