NDLI: Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro

Content Provider	PubMed Central
Author	Li, Yu-huan Tao, Pei-zhen Liu, Yu-zhen Jiang, Jian-dong
Copyright Year	2004
Abstract	Geldanamycin (GA) is an antibiotic targeting the ADP/ATP binding site of heat shock protein 90 (Hsp90). In screening for anti-herpes simplex virus type 1 (HSV-1) candidates, we found GA active against HSV-1. HSV-1 replication in vitro was significantly inhibited by GA with an 50% inhibitory concentration of 0.093 μM and a concentration that inhibited cellular growth 50% in comparison with the results seen with untreated controls of 350 μM. The therapeutic index of GA was over 3,700 (comparable to the results seen with acyclovir). GA did not inhibit HSV-1 thymidine kinase. Cells infected with HSV-1 demonstrated cell cycle arrest at the G1/S transition; however, treatment with GA resulted in a cell cycle distribution pattern identical to that of untreated cells, indicating a restoration of cell growth in HSV-1-infected cells by GA treatment. Accordingly, HSV-1 DNA synthesis was suppressed in HSV-1+ cells treated with GA. The antiviral mechanism of GA appears to be associated with Hsp90 inactivation and cell cycle restoration, which indicates that GA exhibits broad-spectrum antiviral activity. Indeed, GA exhibited activities in vitro against other viruses, including severe acute respiratory syndrome coronavirus. Since GA inhibits HSV-1 through a cellular mechanism unique among HSV-1 agents, we consider it a new candidate agent for HSV-1.
Related Links	http://dx.doi.org/10.1128/aac.48.3.867-872.2004
Ending Page	872
Page Count	6
Starting Page	867
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	3
Volume Number	48
Language	English
Publisher	American Society for Microbiology
Publisher Date	2004-03-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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