Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs
Open Access
- 18 March 2021
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 65 (4)
- https://doi.org/10.1128/aac.01146-20
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.Keywords
Funding Information
- HHS | National Institutes of Health (AI114776)
- HHS | National Institutes of Health (AI119142)
- Washington Research Foundation
This publication has 79 references indexed in Scilit:
- Pharmacokinetics of single and multiple oral doses of arbidol in healthy Chinese volunteersInt. Journal of Clinical Pharmacology and Therapeutics, 2013
- Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral EffectsPLoS Pathogens, 2012
- Standardizing immunophenotyping for the Human Immunology ProjectNature Reviews Immunology, 2012
- Evaluation of Lassa antiviral compound ST-193 in a guinea pig modelAntiviral Research, 2011
- Synergistic drug combinations tend to improve therapeutically relevant selectivityNature Biotechnology, 2009
- pH-Induced Activation of Arenavirus Membrane Fusion Is Antagonized by Small-Molecule InhibitorsJournal of Virology, 2008
- Inhibition of T-Cell Inflammatory Cytokines, Hepatocyte NF-κB Signaling, and HCV Infection by Standardized SilymarinGastroenterology, 2007
- Biochemical Mechanism of Hepatitis C Virus Inhibition by the Broad-Spectrum Antiviral ArbidolBiochemistry, 2007
- Mitigation strategies for pandemic influenza in the United StatesProceedings of the National Academy of Sciences of the United States of America, 2006
- Clinical Pharmacokinetics of SertralineClinical Pharmacokinetics, 2002