Identification of a small-molecule inhibitor of dengue virus using a replicon system

Identification of a small-molecule inhibitor of dengue virus using a replicon system Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Identification of a small-molecule inhibitor of dengue virus using a replicon system

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Publisher
Springer Journals
Copyright
Copyright © 2012 by Springer-Verlag
Subject
Biomedicine; Infectious Diseases; Medical Microbiology; Virology
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-012-1224-z
Publisher site
See Article on Publisher Site

Abstract

Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication.

Journal

Archives of VirologySpringer Journals

Published: Apr 1, 2012

References

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