The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within Fibroblasts
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus for which there is no vaccine or cure. This viral infection, once acquired, is life-long, residing latently in hematopoietic cells. However, latently infected individuals with weakened immune systems often undergo HCMV reactivation, which can...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/10/11/614 |
| _version_ | 1819052990090182656 |
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| author | Masatoshi Nukui Christine M. O’Connor Eain A. Murphy |
| author_facet | Masatoshi Nukui Christine M. O’Connor Eain A. Murphy |
| author_sort | Masatoshi Nukui |
| collection | DOAJ |
| description | Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus for which there is no vaccine or cure. This viral infection, once acquired, is life-long, residing latently in hematopoietic cells. However, latently infected individuals with weakened immune systems often undergo HCMV reactivation, which can cause serious complications in immunosuppressed and immunocompromised patients. Current anti-viral therapies target late stages of viral replication, and are often met with therapeutic resistance, necessitating the development of novel therapeutics. In this current study, we identified a naturally-occurring flavonoid compound, deguelin, which inhibits HCMV lytic replication. Our findings reveal that nanomolar concentrations of deguelin significantly suppress the production of the infectious virus. Further, we show that deguelin inhibits the lytic cycle during the phase of the replication cycle consistent with early (E) gene and protein expression. Importantly, our data reveal that deguelin inhibits replication of a ganciclovir-resistant strain of HCMV. Together, our findings identify a novel, naturally occurring compound that may prove useful in the treatment of HCMV replication. |
| first_indexed | 2024-12-21T12:28:36Z |
| format | Article |
| id | doaj.art-a2ebf891e9f24803a801408f7d7e1f75 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-21T12:28:36Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a2ebf891e9f24803a801408f7d7e1f752022-12-21T19:04:06ZengMDPI AGViruses1999-49152018-11-01101161410.3390/v10110614v10110614The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within FibroblastsMasatoshi Nukui0Christine M. O’Connor1Eain A. Murphy2Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USAGenomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USAFORGE Life Science, Pennsylvania Biotechnology Center, Doylestown, PA 18901, USAHuman cytomegalovirus (HCMV) is a ubiquitous herpesvirus for which there is no vaccine or cure. This viral infection, once acquired, is life-long, residing latently in hematopoietic cells. However, latently infected individuals with weakened immune systems often undergo HCMV reactivation, which can cause serious complications in immunosuppressed and immunocompromised patients. Current anti-viral therapies target late stages of viral replication, and are often met with therapeutic resistance, necessitating the development of novel therapeutics. In this current study, we identified a naturally-occurring flavonoid compound, deguelin, which inhibits HCMV lytic replication. Our findings reveal that nanomolar concentrations of deguelin significantly suppress the production of the infectious virus. Further, we show that deguelin inhibits the lytic cycle during the phase of the replication cycle consistent with early (E) gene and protein expression. Importantly, our data reveal that deguelin inhibits replication of a ganciclovir-resistant strain of HCMV. Together, our findings identify a novel, naturally occurring compound that may prove useful in the treatment of HCMV replication.https://www.mdpi.com/1999-4915/10/11/614cytomegalovirusHCMVdeguelinganciclovir |
| spellingShingle | Masatoshi Nukui Christine M. O’Connor Eain A. Murphy The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within Fibroblasts Viruses cytomegalovirus HCMV deguelin ganciclovir |
| title | The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within Fibroblasts |
| title_full | The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within Fibroblasts |
| title_fullStr | The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within Fibroblasts |
| title_full_unstemmed | The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within Fibroblasts |
| title_short | The Natural Flavonoid Compound Deguelin Inhibits HCMV Lytic Replication within Fibroblasts |
| title_sort | natural flavonoid compound deguelin inhibits hcmv lytic replication within fibroblasts |
| topic | cytomegalovirus HCMV deguelin ganciclovir |
| url | https://www.mdpi.com/1999-4915/10/11/614 |
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