5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells
Baicalin, a bioactive flavone found in Scutellaria baicalensis Georgi has anti-SARS-CoV-2 infection by targeting viral 3C-like protease (3CLpro). However, little is known about the antiviral activity of its 7-deoxy analogue, 5,6-dihydroxyflavone (5,6-DHF), especially against betacoronaviruses (beta-...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | Virus Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168170225000553 |
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| author | Yujia Cao Kah Man Lai Hongling Zheng Yee Joo Tan Dejian Huang |
| author_facet | Yujia Cao Kah Man Lai Hongling Zheng Yee Joo Tan Dejian Huang |
| author_sort | Yujia Cao |
| collection | DOAJ |
| description | Baicalin, a bioactive flavone found in Scutellaria baicalensis Georgi has anti-SARS-CoV-2 infection by targeting viral 3C-like protease (3CLpro). However, little is known about the antiviral activity of its 7-deoxy analogue, 5,6-dihydroxyflavone (5,6-DHF), especially against betacoronaviruses (beta-CoVs). We found that 5,6-DHF exhibited more potent anti-SARS-CoV-2 Omicron variant EG.5.1.1 activity than baicalein by microneutralization test (MNT) and plaque reduction neutralization test (PRNT). 5,6-Dihydroxyl (catechol) groups at A ring of 5,6-DHF is essential for its suppression on SARS-CoV-2 Omicron variant EG.5.1.1 infection because blocking them with methyl or methylene groups obsolesce the activity. 3CLpro inhibition assay showed that the antiviral activity of 5,6-DHF is distinctive with baicalein. Time of addition test, molecular docking and spike-bearing pseudotyped virus entry assay suggested that 5,6-DHF interferes the spike-ACE2 interaction by targeting at receptor binding domain (RBD) of spike and hence inhibits the virus replication. In addition to SARS-CoV-2 Omicron variant EG.5.1.1, 5,6-DHF was also found effective against another common human beta-CoVs, HCoV-OC43, by blocking their entry to host cells. Taken together, the present study demonstrated the potential function of 5,6-DHF as a therapeutic candidate against beta-CoVs. |
| format | Article |
| id | doaj-art-46c7c8bbe7a24dc99a1c1e3ec9e4a919 |
| institution | Kabale University |
| issn | 1872-7492 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Virus Research |
| spelling | doaj-art-46c7c8bbe7a24dc99a1c1e3ec9e4a9192025-08-20T03:47:41ZengElsevierVirus Research1872-74922025-06-0135619957810.1016/j.virusres.2025.1995785,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cellsYujia Cao0Kah Man Lai1Hongling Zheng2Yee Joo Tan3Dejian Huang4Department of Food Science and Technology, National University of Singapore, Singapore 117542, SingaporeInfectious Diseases Translational Research Program and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeDepartment of Food Science and Technology, National University of Singapore, Singapore 117542, SingaporeInfectious Diseases Translational Research Program and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore; Corresponding authors.Department of Food Science and Technology, National University of Singapore, Singapore 117542, Singapore; National University of Singapore (Suzhou) Research Institute, 377 Linquan Street, Suzhou 215123, PR China; Corresponding authors.Baicalin, a bioactive flavone found in Scutellaria baicalensis Georgi has anti-SARS-CoV-2 infection by targeting viral 3C-like protease (3CLpro). However, little is known about the antiviral activity of its 7-deoxy analogue, 5,6-dihydroxyflavone (5,6-DHF), especially against betacoronaviruses (beta-CoVs). We found that 5,6-DHF exhibited more potent anti-SARS-CoV-2 Omicron variant EG.5.1.1 activity than baicalein by microneutralization test (MNT) and plaque reduction neutralization test (PRNT). 5,6-Dihydroxyl (catechol) groups at A ring of 5,6-DHF is essential for its suppression on SARS-CoV-2 Omicron variant EG.5.1.1 infection because blocking them with methyl or methylene groups obsolesce the activity. 3CLpro inhibition assay showed that the antiviral activity of 5,6-DHF is distinctive with baicalein. Time of addition test, molecular docking and spike-bearing pseudotyped virus entry assay suggested that 5,6-DHF interferes the spike-ACE2 interaction by targeting at receptor binding domain (RBD) of spike and hence inhibits the virus replication. In addition to SARS-CoV-2 Omicron variant EG.5.1.1, 5,6-DHF was also found effective against another common human beta-CoVs, HCoV-OC43, by blocking their entry to host cells. Taken together, the present study demonstrated the potential function of 5,6-DHF as a therapeutic candidate against beta-CoVs.http://www.sciencedirect.com/science/article/pii/S0168170225000553Anti-coronavirus5,6-dihydroxyflavoneReceptor-binding domainFlavonesSars-cov-2 |
| spellingShingle | Yujia Cao Kah Man Lai Hongling Zheng Yee Joo Tan Dejian Huang 5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells Virus Research Anti-coronavirus 5,6-dihydroxyflavone Receptor-binding domain Flavones Sars-cov-2 |
| title | 5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells |
| title_full | 5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells |
| title_fullStr | 5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells |
| title_full_unstemmed | 5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells |
| title_short | 5,6-dihydroxyflavone exerts anti-betacoronavirus activity by blocking viral entry to host cells |
| title_sort | 5 6 dihydroxyflavone exerts anti betacoronavirus activity by blocking viral entry to host cells |
| topic | Anti-coronavirus 5,6-dihydroxyflavone Receptor-binding domain Flavones Sars-cov-2 |
| url | http://www.sciencedirect.com/science/article/pii/S0168170225000553 |
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