FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells
Vector-borne flaviviruses (VBFs) affect human health worldwide, but no approved drugs are available specifically to treat VBF-associated infections. Here, we performed in silico screening of a library of U.S. Food and Drug Administration-approved antiviral drugs for their interaction with Zika virus...
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MDPI AG
2020-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/4/599 |
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| author | Michal Stefanik James J. Valdes Fortunatus C. Ezebuo Jan Haviernik Ikemefuna C. Uzochukwu Martina Fojtikova Jiri Salat Ludek Eyer Daniel Ruzek |
| author_facet | Michal Stefanik James J. Valdes Fortunatus C. Ezebuo Jan Haviernik Ikemefuna C. Uzochukwu Martina Fojtikova Jiri Salat Ludek Eyer Daniel Ruzek |
| author_sort | Michal Stefanik |
| collection | DOAJ |
| description | Vector-borne flaviviruses (VBFs) affect human health worldwide, but no approved drugs are available specifically to treat VBF-associated infections. Here, we performed in silico screening of a library of U.S. Food and Drug Administration-approved antiviral drugs for their interaction with Zika virus proteins. Twelve hit drugs were identified by the docking experiments and tested in cell-based antiviral assay systems. Efavirenz, tipranavir, and dasabuvir at micromolar concentrations were identified to inhibit all VBFs tested; i.e., two representatives of mosquito-borne flaviviruses (Zika and West Nile viruses) and one representative of flaviviruses transmitted by ticks (tick-borne encephalitis virus). The results warrant further research into these drugs, either individually or in combination, as possible pan-flavivirus inhibitors. |
| first_indexed | 2024-03-10T20:20:33Z |
| format | Article |
| id | doaj.art-aeee10316a554a17882b166a2eaec000 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T20:20:33Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-aeee10316a554a17882b166a2eaec0002023-11-19T22:13:39ZengMDPI AGMicroorganisms2076-26072020-04-018459910.3390/microorganisms8040599FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero CellsMichal Stefanik0James J. Valdes1Fortunatus C. Ezebuo2Jan Haviernik3Ikemefuna C. Uzochukwu4Martina Fojtikova5Jiri Salat6Ludek Eyer7Daniel Ruzek8Department of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicDepartment of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicDepartment of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, PMB 5025 Awka 420281, NigeriaDepartment of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicDepartment of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, PMB 5025 Awka 420281, NigeriaDepartment of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicDepartment of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicDepartment of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicDepartment of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicVector-borne flaviviruses (VBFs) affect human health worldwide, but no approved drugs are available specifically to treat VBF-associated infections. Here, we performed in silico screening of a library of U.S. Food and Drug Administration-approved antiviral drugs for their interaction with Zika virus proteins. Twelve hit drugs were identified by the docking experiments and tested in cell-based antiviral assay systems. Efavirenz, tipranavir, and dasabuvir at micromolar concentrations were identified to inhibit all VBFs tested; i.e., two representatives of mosquito-borne flaviviruses (Zika and West Nile viruses) and one representative of flaviviruses transmitted by ticks (tick-borne encephalitis virus). The results warrant further research into these drugs, either individually or in combination, as possible pan-flavivirus inhibitors.https://www.mdpi.com/2076-2607/8/4/599FDAflavivirusZika virustick-borne encephalitis virusWest Nile virusantiviral |
| spellingShingle | Michal Stefanik James J. Valdes Fortunatus C. Ezebuo Jan Haviernik Ikemefuna C. Uzochukwu Martina Fojtikova Jiri Salat Ludek Eyer Daniel Ruzek FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells Microorganisms FDA flavivirus Zika virus tick-borne encephalitis virus West Nile virus antiviral |
| title | FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells |
| title_full | FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells |
| title_fullStr | FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells |
| title_full_unstemmed | FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells |
| title_short | FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells |
| title_sort | fda approved drugs efavirenz tipranavir and dasabuvir inhibit replication of multiple flaviviruses in vero cells |
| topic | FDA flavivirus Zika virus tick-borne encephalitis virus West Nile virus antiviral |
| url | https://www.mdpi.com/2076-2607/8/4/599 |
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