Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor
Drug repurposing can quickly and effectively identify novel drug repurposing opportunities. The PA endonuclease catalytic site has recently become regarded as an attractive target for the screening of anti-influenza drugs. PA N-terminal (PA<sub>N</sub>) inhibitor can inhibit the entire P...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/23/7326 |
| _version_ | 1797507330114322432 |
|---|---|
| author | Xin Meng Ye Wang |
| author_facet | Xin Meng Ye Wang |
| author_sort | Xin Meng |
| collection | DOAJ |
| description | Drug repurposing can quickly and effectively identify novel drug repurposing opportunities. The PA endonuclease catalytic site has recently become regarded as an attractive target for the screening of anti-influenza drugs. PA N-terminal (PA<sub>N</sub>) inhibitor can inhibit the entire PA endonuclease activity. In this study, we screened the effectivity of PA<sub>N</sub> inhibitors from the FDA database through in silico methods and in vitro experiments. PA<sub>N</sub> and mutant PA<sub>N</sub>-I38T were chosen as virtual screening targets for overcoming drug resistance. Gel-based PA endonuclease analysis determined that the drug lifitegrast can effectively inhibit PA<sub>N</sub> and PA<sub>N</sub>-I38T, when the IC<sub>50</sub> is 32.82 ± 1.34 μM and 26.81 ± 1.2 μM, respectively. Molecular docking calculation showed that lifitegrast interacted with the residues around PA or PA-I38 T’s active site, occupying the catalytic site pocket. Both PA<sub>N</sub>/PA<sub>N</sub>-I38T and lifitegrast can acquire good equilibrium in 100 ns molecular dynamic simulation. Because of these properties, lifitegrast, which can effectively inhibit PA endonuclease activity, was screened through in silico and in vitro research. This new research will be of significance in developing more effective and selective drugs for anti-influenza therapy. |
| first_indexed | 2024-03-10T04:47:00Z |
| format | Article |
| id | doaj.art-07c3d7c41823492eb5930cbc30888d96 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T04:47:00Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-07c3d7c41823492eb5930cbc30888d962023-11-23T02:50:47ZengMDPI AGMolecules1420-30492021-12-012623732610.3390/molecules26237326Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease InhibitorXin Meng0Ye Wang1School of Life Science, Jilin University, No. 2699 Qianjin Street, Changchun 130012, ChinaSchool of Life Science, Jilin University, No. 2699 Qianjin Street, Changchun 130012, ChinaDrug repurposing can quickly and effectively identify novel drug repurposing opportunities. The PA endonuclease catalytic site has recently become regarded as an attractive target for the screening of anti-influenza drugs. PA N-terminal (PA<sub>N</sub>) inhibitor can inhibit the entire PA endonuclease activity. In this study, we screened the effectivity of PA<sub>N</sub> inhibitors from the FDA database through in silico methods and in vitro experiments. PA<sub>N</sub> and mutant PA<sub>N</sub>-I38T were chosen as virtual screening targets for overcoming drug resistance. Gel-based PA endonuclease analysis determined that the drug lifitegrast can effectively inhibit PA<sub>N</sub> and PA<sub>N</sub>-I38T, when the IC<sub>50</sub> is 32.82 ± 1.34 μM and 26.81 ± 1.2 μM, respectively. Molecular docking calculation showed that lifitegrast interacted with the residues around PA or PA-I38 T’s active site, occupying the catalytic site pocket. Both PA<sub>N</sub>/PA<sub>N</sub>-I38T and lifitegrast can acquire good equilibrium in 100 ns molecular dynamic simulation. Because of these properties, lifitegrast, which can effectively inhibit PA endonuclease activity, was screened through in silico and in vitro research. This new research will be of significance in developing more effective and selective drugs for anti-influenza therapy.https://www.mdpi.com/1420-3049/26/23/7326lifitegrastvirtual screeningdrug repurposing |
| spellingShingle | Xin Meng Ye Wang Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor Molecules lifitegrast virtual screening drug repurposing |
| title | Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor |
| title_full | Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor |
| title_fullStr | Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor |
| title_full_unstemmed | Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor |
| title_short | Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor |
| title_sort | drug repurposing for influenza virus polymerase acidic pa endonuclease inhibitor |
| topic | lifitegrast virtual screening drug repurposing |
| url | https://www.mdpi.com/1420-3049/26/23/7326 |
| work_keys_str_mv | AT xinmeng drugrepurposingforinfluenzaviruspolymeraseacidicpaendonucleaseinhibitor AT yewang drugrepurposingforinfluenzaviruspolymeraseacidicpaendonucleaseinhibitor |