Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity
Abstract Herpes simplex virus type 2 (HSV-2) is a highly prevalent human pathogen worldwide that not only causes genital herpes but is also associated with severe health complications, such as neonatal infections and increased susceptibility to HIV. Currently, due to the lack of an effective HSV-2 v...
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BMC
2025-07-01
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| Online Access: | https://doi.org/10.1186/s12985-025-02867-8 |
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| author | Songshan Li Minghan Li Yantong Cai Jun Xian Rongrong Zhu Chan Yang Xin Zhang Shuya Ren Aijiao Yu Shuwen Liu Bin Yang |
| author_facet | Songshan Li Minghan Li Yantong Cai Jun Xian Rongrong Zhu Chan Yang Xin Zhang Shuya Ren Aijiao Yu Shuwen Liu Bin Yang |
| author_sort | Songshan Li |
| collection | DOAJ |
| description | Abstract Herpes simplex virus type 2 (HSV-2) is a highly prevalent human pathogen worldwide that not only causes genital herpes but is also associated with severe health complications, such as neonatal infections and increased susceptibility to HIV. Currently, due to the lack of an effective HSV-2 vaccine and the emergence of more drug-resistant strains, there is an urgent need to develop effective, safe, and affordable anti-HSV-2 medications. The small molecule UCM05 is a novel inhibitor of fatty acid synthase (FASN) and filamentous temperature-sensitive protein Z (Ftsz), with antitumor and antibacterial effects. In this study, we found that UCM05 effectively inhibits both HSV-2 and acyclovir-resistant HSV-2 infections in vitro, significantly improves survival rates in HSV-2-infected mice, and effectively reduces viral titers in tissues. Further, we discovered that UCM05 destroys the membrane integrity of viral particles by directly binding with HSV-2 glycoproteins gB and gD and reduces viral replication by inhibiting viral protein synthesis and fatty acid synthesis. Additionally, UCM05 treatment promoted the generation of type I IFN related genes but does not result in an inflammatory cytokine storm triggered by HSV-2, and it also exhibited activity against co-infection with HIV-1/HSV-2, as well as infection with HSV-1. Overall, our research demonstrates that UCM05 can effectively inhibit HSV-2 infection both in vitro and in vivo. UCM05 represents a potential new antiviral drug against HSV-2. |
| format | Article |
| id | doaj-art-d9f75e8a7ce740b4ba0d570a3080c23e |
| institution | DOAJ |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-d9f75e8a7ce740b4ba0d570a3080c23e2025-08-20T03:04:10ZengBMCVirology Journal1743-422X2025-07-0122111910.1186/s12985-025-02867-8Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunitySongshan Li0Minghan Li1Yantong Cai2Jun Xian3Rongrong Zhu4Chan Yang5Xin Zhang6Shuya Ren7Aijiao Yu8Shuwen Liu9Bin Yang10Dermatology Hospital, Southern Medical UniversityThe People’s Hospital of Baiyun District GuangzhouDermatology Hospital, Southern Medical UniversityDermatology Hospital, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityDepartment of Pharmaceutics, The Second Affiliated Hospital of Dalian Medical University DalianDermatology Hospital, Southern Medical UniversityDermatology Hospital, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityDermatology Hospital, Southern Medical UniversityAbstract Herpes simplex virus type 2 (HSV-2) is a highly prevalent human pathogen worldwide that not only causes genital herpes but is also associated with severe health complications, such as neonatal infections and increased susceptibility to HIV. Currently, due to the lack of an effective HSV-2 vaccine and the emergence of more drug-resistant strains, there is an urgent need to develop effective, safe, and affordable anti-HSV-2 medications. The small molecule UCM05 is a novel inhibitor of fatty acid synthase (FASN) and filamentous temperature-sensitive protein Z (Ftsz), with antitumor and antibacterial effects. In this study, we found that UCM05 effectively inhibits both HSV-2 and acyclovir-resistant HSV-2 infections in vitro, significantly improves survival rates in HSV-2-infected mice, and effectively reduces viral titers in tissues. Further, we discovered that UCM05 destroys the membrane integrity of viral particles by directly binding with HSV-2 glycoproteins gB and gD and reduces viral replication by inhibiting viral protein synthesis and fatty acid synthesis. Additionally, UCM05 treatment promoted the generation of type I IFN related genes but does not result in an inflammatory cytokine storm triggered by HSV-2, and it also exhibited activity against co-infection with HIV-1/HSV-2, as well as infection with HSV-1. Overall, our research demonstrates that UCM05 can effectively inhibit HSV-2 infection both in vitro and in vivo. UCM05 represents a potential new antiviral drug against HSV-2.https://doi.org/10.1186/s12985-025-02867-8UCM05HSV-2Entry inhibitionFatty acid synthesisImmune enhancementCo-infections |
| spellingShingle | Songshan Li Minghan Li Yantong Cai Jun Xian Rongrong Zhu Chan Yang Xin Zhang Shuya Ren Aijiao Yu Shuwen Liu Bin Yang Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity Virology Journal UCM05 HSV-2 Entry inhibition Fatty acid synthesis Immune enhancement Co-infections |
| title | Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity |
| title_full | Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity |
| title_fullStr | Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity |
| title_full_unstemmed | Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity |
| title_short | Small molecule UCM05 inhibits HSV-2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity |
| title_sort | small molecule ucm05 inhibits hsv 2 infection via targeting viral glycoproteins and fatty acid synthase with potentiating antiviral immunity |
| topic | UCM05 HSV-2 Entry inhibition Fatty acid synthesis Immune enhancement Co-infections |
| url | https://doi.org/10.1186/s12985-025-02867-8 |
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