HTS-driven discovery of new chemotypes with West Nile Virus inhibitory activity.
Molecules
; 15(3): 1690-704, 2010 Mar 12.
Article
em En
| MEDLINE
| ID: mdl-20336008
West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 microM final concentration was conducted using the 384-well format. Z' values ranged from 0.54-0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírus do Nilo Ocidental
Limite:
Animals
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos