Abstract |
The number of disseminated adenovirus (Ad) infections continues to increase mostly due to the growing use of immunosuppressive treatments. Recipients of solid organ or hematopoietic stem cell transplants, mainly in pediatric units, exhibit a high morbidity and mortality due to these infections. Unfortunately, there are no Ad-specific antiviral drugs currently approved for medical use. To address this situation, we used high-throughput screening (HTS) of synthetic small molecule libraries to identify compounds that restrict Ad infection. Among the more than 25,000 compounds screened, we identified a hit compound that significantly inhibited Ad infection. The compound (15D8) is a trisubstituted piperazin-2-one derivative that showed substantial antiviral activity with little or no cytotoxicity at low micromolar concentrations. Compound 15D8 selectively inhibits Ad DNA replication in the nucleus, providing a potential candidate for the development of a new class of antiviral compounds to treat Ad infections.
|
Authors | Javier Sanchez-Cespedes, Crystal L Moyer, Landon R Whitby, Dale L Boger, Glen R Nemerow |
Journal | Antiviral research
(Antiviral Res)
Vol. 108
Pg. 65-73
(Aug 2014)
ISSN: 1872-9096 [Electronic] Netherlands |
PMID | 24907427
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2014 Elsevier B.V. All rights reserved. |
Chemical References |
- Antiviral Agents
- Piperazines
|
Topics |
- Adenoviridae
(drug effects, physiology)
- Antiviral Agents
(chemistry, isolation & purification, pharmacology, toxicity)
- Cell Line
- Cell Survival
(drug effects)
- Drug Evaluation, Preclinical
(methods)
- High-Throughput Screening Assays
- Humans
- Inhibitory Concentration 50
- Piperazines
(chemistry, isolation & purification, pharmacology, toxicity)
- Viral Plaque Assay
- Virus Replication
(drug effects)
|