HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity
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 throughp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2010-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/15/3/1690/ |
| _version_ | 1831727433910321152 |
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| author | Qianjun Li Shuang Feng Marintha Heil E. Lucile White Subramaniam Ananthan Blake. P. Moore Sara N. McKellip Clinton Maddox Colleen B. Jonsson Dong Hoon Chung Lynn Rasmussen |
| author_facet | Qianjun Li Shuang Feng Marintha Heil E. Lucile White Subramaniam Ananthan Blake. P. Moore Sara N. McKellip Clinton Maddox Colleen B. Jonsson Dong Hoon Chung Lynn Rasmussen |
| author_sort | Qianjun Li |
| collection | DOAJ |
| description | 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 µM 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. |
| first_indexed | 2024-12-21T06:29:01Z |
| format | Article |
| id | doaj.art-5c904eff5d7f424cbbe5b45e003c5992 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T06:29:01Z |
| publishDate | 2010-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5c904eff5d7f424cbbe5b45e003c59922022-12-21T19:13:02ZengMDPI AGMolecules1420-30492010-03-011531690170410.3390/molecules15031690HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory ActivityQianjun LiShuang FengMarintha HeilE. Lucile WhiteSubramaniam AnanthanBlake. P. MooreSara N. McKellipClinton MaddoxColleen B. JonssonDong Hoon ChungLynn RasmussenWest 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 µM 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.http://www.mdpi.com/1420-3049/15/3/1690/West Nile virushigh throughput screenantiviralschemotypes |
| spellingShingle | Qianjun Li Shuang Feng Marintha Heil E. Lucile White Subramaniam Ananthan Blake. P. Moore Sara N. McKellip Clinton Maddox Colleen B. Jonsson Dong Hoon Chung Lynn Rasmussen HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity Molecules West Nile virus high throughput screen antivirals chemotypes |
| title | HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity |
| title_full | HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity |
| title_fullStr | HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity |
| title_full_unstemmed | HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity |
| title_short | HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity |
| title_sort | hts driven discovery of new chemotypes with west nile virus inhibitory activity |
| topic | West Nile virus high throughput screen antivirals chemotypes |
| url | http://www.mdpi.com/1420-3049/15/3/1690/ |
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