Abstract |
Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants and young children worldwide, yet no vaccine or effective antiviral treatment is available. To search for new anti-RSV agents, we developed a cell-based assay that measures inhibition of RSV-induced cytopathic effect (CPE) and identified cyclopiazonic acid (CPA), an intracellular calcium ATPase inhibitor as a RSV inhibitor (EC50 values 4.13 μM) by screening of natural product library. CPA inhibited the replication of RSV strains belonging to both A and B subgroups and human parainfluenza virus type 3, but not Enterovirus 71. Mechanism of action study by time-of-addition assay and minigenome assay revealed that CPA acts at the step of virus genome replication and/or transcription. Moreover, two other calcium ATPase inhibitors ( Thapsigargin and BHQ) and calcium ionophores ( A23187 and ionomycin), but not calcium channel blockers ( nifedipine, nimodipine, and tetrandrine), also had similar effect. These results indicate that an increase in intracellular calcium concentration is detrimental to RSV replication. Thus, our findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration.
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Authors | Rui Cui, Yizhuo Wang, Liu Wang, Guiming Li, Ke Lan, Ralf Altmeyer, Gang Zou |
Journal | Antiviral research
(Antiviral Res)
Vol. 132
Pg. 38-45
(08 2016)
ISSN: 1872-9096 [Electronic] Netherlands |
PMID | 27210812
(Publication Type: Journal Article)
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Copyright | Copyright © 2016 Elsevier B.V. All rights reserved. |
Chemical References |
- Antiviral Agents
- Biological Products
- Indoles
- Small Molecule Libraries
- Calcium-Transporting ATPases
- Sodium-Potassium-Exchanging ATPase
- Calcium
- cyclopiazonic acid
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Topics |
- Animals
- Antiviral Agents
(chemistry, pharmacology)
- Biological Products
(pharmacology)
- Calcium
(metabolism)
- Calcium-Transporting ATPases
(antagonists & inhibitors)
- Cell Line
- Dose-Response Relationship, Drug
- Gene Expression Regulation, Viral
(drug effects)
- High-Throughput Screening Assays
- Humans
- Indoles
(chemistry, pharmacology)
- Respiratory Syncytial Virus Infections
(metabolism, virology)
- Respiratory Syncytial Virus, Human
(drug effects, physiology)
- Small Molecule Libraries
- Sodium-Potassium-Exchanging ATPase
(antagonists & inhibitors)
- Virus Replication
(drug effects)
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