scholarly journals Geldanamycin, a ligand of heat shock protein 90, inhibits herpes simplex virus type 2 replication both in vitro and in vivo

2012 ◽  
Vol 65 (10) ◽  
pp. 509-512 ◽  
Author(s):  
Yu-Huan Li ◽  
Qiao-Ni Lu ◽  
Hui-Qiang Wang ◽  
Pei-Zhen Tao ◽  
Jian-Dong Jiang
2008 ◽  
Vol 15 (5) ◽  
pp. 773-782 ◽  
Author(s):  
David M. Koelle ◽  
Amalia Magaret ◽  
Christopher L. McClurkan ◽  
Michael L. Remington ◽  
Terri Warren ◽  
...  

ABSTRACT This was a phase I study to assess the safety, tolerability, and immunogenicity of escalating doses of AG-702, a noncovalent complex of an HLA A*0201-restricted epitope in the glycoprotein B protein of herpes simplex virus type 2 (gB2) and truncated human constitutive heat shock protein 70. Similar vaccines have been immunogenic in animals. Three injections of 10 to 250 μg were administered intradermally to HLA A*0201-bearing subjects who were either herpes simplex virus type 2 (HSV-2)-infected or HSV uninfected. Sixty-two participants received the vaccine, 60 completed the protocol, and T-cell data were accrued for 56 subjects. The vaccine was safe and well tolerated. New or boosted responses to the HSV-2 CD8 epitope were not detected. Baseline responses to an epitope in virion proteins 13/14 were higher than responses to the gB2 epitope. A heat shock protein vaccine with an HSV-2 peptide appears to be safe at the doses studied in healthy adults with or without HSV infection. Modifications of the dose, adjuvant, route, schedule, or HSV antigen may be required to improve responses.


2004 ◽  
Vol 48 (3) ◽  
pp. 867-872 ◽  
Author(s):  
Yu-Huan Li ◽  
Pei-Zhen Tao ◽  
Yu-Zhen Liu ◽  
Jian-Dong Jiang

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.


Viruses ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 119 ◽  
Author(s):  
Wenwen Dai ◽  
Yu Wu ◽  
Jinpeng Bi ◽  
Shuai Wang ◽  
Fang Li ◽  
...  

Author(s):  
N. V. Krylova ◽  
I. A. Leneva ◽  
S. A. Fedoreev ◽  
L. K. Ebralidze ◽  
N. P. Mishchenko ◽  
...  

The aim of the work was to study the activity of echinochrome A, a naphthoquinoid pigment from sea urchins, and its antioxidant composition against herpes simplex virus type 2 (HSV-2) in vitro and in vivo.Materials and methods. Strain HSV-2 (G ATCC VR-734) was grown in Vero cells. The cytotoxic and anti-HSV-2 activity of the compounds was assessed in vitro by the cell viability and by cytopathic effect inhibition of virus using MTT test. The efficacy of compounds in mice model of vaginitis caused by HSV-2 was determined by the average lifetime, body weight and viral load changes.Results and discussion. The antioxidant composition (echinochrome A, ascorbic acid and α-tocopherol (5:5:1)), showed a higher antiviral efficacy than echinochrome A alone. Oral administration of the antioxidant composition protected 90% of the infected mice against death and reduced vaginal viral loads. The antiviral activity of echinochrome A and the antioxidant composition is probably due to the virus-inhibiting activity of the compounds and their antioxidant properties.Conclusion. The results obtained allow considering the tested compounds as promising agents with antiviral properties.


Virology ◽  
2003 ◽  
Vol 314 (1) ◽  
pp. 147-160 ◽  
Author(s):  
L Fang ◽  
M.G Ward ◽  
P.A Welsh ◽  
L.R Budgeon ◽  
E.B Neely ◽  
...  

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