Li YH, Tao PZ, Liu YZ, Jiang JD.Geldanamycin, a ligand of
heat shock protein 90, inhibits the replication of herpes
simplex virus type 1 in vitro.
Antimicrob Agents Chemother. 2004 Mar;48(3):867-72.
Laboratory of Antiviral Research, Institute of Medicinal
Biotechnology, Chinese Academy of Medical Sciences and Peking
Union Medical College, Beijing 100050, People's Republic of
China.
Geldanamycin 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 Geldanamycin
active against HSV-1. HSV-1 replication in vitro was
significantly inhibited by Geldanamycin with an 50% inhibitory
concentration of 0.093 microM and a concentration that inhibited
cellular growth 50% in comparison with the results seen with
untreated controls of 350 microM. The therapeutic index of
Geldanamycin was over 3700 (comparable to the results seen with
acyclovir). Geldanamycin did not inhibit HSV-1 thymidine kinase.
Cells infected with HSV-1 demonstrated cell cycle arrest at the
G(1)/S transition; however, treatment with Geldanamycin 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 Geldanamycin treatment. Accordingly,
HSV-1 DNA synthesis was suppressed in HSV-1(+) cells treated
with Geldanamycin . The antiviral mechanism of Geldanamycin
appears to be associated with Hsp90 inactivation and cell cycle
restoration, which indicates that Geldanamycin exhibits
broad-spectrum antiviral activity. Indeed, Geldanamycin
exhibited activities in vitro vs other viruses, including severe
acute respiratory syndrome coronavirus. Since Geldanamycin
inhibits HSV-1 through a cellular mechanism unique among HSV-1
agents, we consider it a new candidate agent for HSV-1.
PMID: 14982777
|
