Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1
Abstract Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains a major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated the potential repurposing of domperidone, an antiemetic and gastro...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87146-w |
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| author | Nuttapong Kaewjiw Thanawat Thaingtamtanha Damini Mehra Wanida Chawnawa Tanapan Prommool Chunya Puttikhunt Adisak Songjaeng Kessiri Kongmanas Panisadee Avirutnan Prasit Luangaram Chatchawan Srisawat Sittiruk Roytrakul Stephan A. Bäurle Sansanee Noisakran |
| author_facet | Nuttapong Kaewjiw Thanawat Thaingtamtanha Damini Mehra Wanida Chawnawa Tanapan Prommool Chunya Puttikhunt Adisak Songjaeng Kessiri Kongmanas Panisadee Avirutnan Prasit Luangaram Chatchawan Srisawat Sittiruk Roytrakul Stephan A. Bäurle Sansanee Noisakran |
| author_sort | Nuttapong Kaewjiw |
| collection | DOAJ |
| description | Abstract Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains a major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated the potential repurposing of domperidone, an antiemetic and gastrokinetic agent, to control DENV infection. Domperidone was identified by pharmacophore-based virtual screening as a small molecule that can bind to both the viral envelope (E) and the nonstructural protein 1 (NS1) of DENV. Molecular dynamics (MD) simulations and surface plasmon resonance (SPR) analysis were subsequently performed to determine specific interactions of domperidone with the DENV E and NS1 proteins and their binding affinity. Treatment of immortalized human hepatocyte-like cells (imHC) with domperidone could inhibit DENV production and NS1 secretion in a dose-dependent manner following infection with DENV serotype 2. These inhibitory effects were mediated by reduction in viral RNA replication and viral E and NS1 protein expression, but not by interference with virus entry into cells or NS1 oligomerization. The suppression of DENV production and NS1 secretion by domperidone was observed across all four DENV serotypes to varying degrees between different virus strains. The findings from our study suggest viral target-based repurposing of domperidone for modulating DENV. |
| format | Article |
| id | doaj-art-61a88b2eedee46398693552f2bc4d2de |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-61a88b2eedee46398693552f2bc4d2de2025-02-02T12:23:34ZengNature PortfolioScientific Reports2045-23222025-01-0115111810.1038/s41598-025-87146-wDomperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1Nuttapong Kaewjiw0Thanawat Thaingtamtanha1Damini Mehra2Wanida Chawnawa3Tanapan Prommool4Chunya Puttikhunt5Adisak Songjaeng6Kessiri Kongmanas7Panisadee Avirutnan8Prasit Luangaram9Chatchawan Srisawat10Sittiruk Roytrakul11Stephan A. Bäurle12Sansanee Noisakran13Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Chemistry and Biology, University of SiegenDepartment of Chemistry and Biology, University of SiegenSiriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol UniversityFunctional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development AgencyDepartment of Chemistry and Biology, University of SiegenSiriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol UniversityAbstract Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains a major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated the potential repurposing of domperidone, an antiemetic and gastrokinetic agent, to control DENV infection. Domperidone was identified by pharmacophore-based virtual screening as a small molecule that can bind to both the viral envelope (E) and the nonstructural protein 1 (NS1) of DENV. Molecular dynamics (MD) simulations and surface plasmon resonance (SPR) analysis were subsequently performed to determine specific interactions of domperidone with the DENV E and NS1 proteins and their binding affinity. Treatment of immortalized human hepatocyte-like cells (imHC) with domperidone could inhibit DENV production and NS1 secretion in a dose-dependent manner following infection with DENV serotype 2. These inhibitory effects were mediated by reduction in viral RNA replication and viral E and NS1 protein expression, but not by interference with virus entry into cells or NS1 oligomerization. The suppression of DENV production and NS1 secretion by domperidone was observed across all four DENV serotypes to varying degrees between different virus strains. The findings from our study suggest viral target-based repurposing of domperidone for modulating DENV.https://doi.org/10.1038/s41598-025-87146-wDengue virusDomperidoneMD simulationE and NS1 proteinsDENV productionNS1 secretion |
| spellingShingle | Nuttapong Kaewjiw Thanawat Thaingtamtanha Damini Mehra Wanida Chawnawa Tanapan Prommool Chunya Puttikhunt Adisak Songjaeng Kessiri Kongmanas Panisadee Avirutnan Prasit Luangaram Chatchawan Srisawat Sittiruk Roytrakul Stephan A. Bäurle Sansanee Noisakran Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1 Scientific Reports Dengue virus Domperidone MD simulation E and NS1 proteins DENV production NS1 secretion |
| title | Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1 |
| title_full | Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1 |
| title_fullStr | Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1 |
| title_full_unstemmed | Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1 |
| title_short | Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1 |
| title_sort | domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1 |
| topic | Dengue virus Domperidone MD simulation E and NS1 proteins DENV production NS1 secretion |
| url | https://doi.org/10.1038/s41598-025-87146-w |
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