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| DOI | 10.1128/jvi.01258-23 |
| Exploring the therapeutic potential of DV-B-120 as an inhibitor of dengue virus infection | |
| Huang, Yi-Jung; Cheng, Tian-Lu; Wang, Yen-Tseng; Chen, Chien-Shu; Leu, Yu-Ling; Chang, Chih-Shiang; Ho, Cheng-Han; Chao, Shi-Wei; Li, Chia-Tse; Chuang, Chih-Hung | |
| 发表日期 | 2024 |
| ISSN | 0022-538X |
| EISSN | 1098-5514 |
| 起始页码 | 98 |
| 结束页码 | 4 |
| 卷号 | 98期号:4 |
| 英文摘要 | Dengue fever, an infectious disease prevalent in subtropical and tropical regions, currently lacks effective small-molecule drugs as treatment. In this study, we used a fluorescence peptide cleavage assay to screen seven compounds to assess their inhibition of the dengue virus (DENV) NS2B-NS3 protease. DV-B-120 demonstrated superior inhibition of NS2B-NS3 protease activity and lower toxicity compared to ARDP0006. The selectivity index of DV-B-120 was higher than that of ARDP0006. In vivo assessments of the antiviral efficacy of DV-B-120 against DENV replication demonstrated delayed mortality of suckling mice treated with the compound, with 60-80% protection against life-threatening effects, compared to the outcomes of DENV-infected mice treated with saline. The lower clinical scores of DENV-infected mice treated with DV-B-120 indicated a reduction in acute-progressive illness symptoms, underscoring the potential therapeutic impact of DV-B-120. Investigations of DV-B-120's ability to restore the antiviral type I IFN response in the brain tissue of DENV-infected ICR suckling mice demonstrated its capacity to stimulate IFN and antiviral IFN-stimulated gene expression. DV-B-120 not only significantly delayed DENV-2-induced mortality and illness symptoms but also reduced viral numbers in the brain, ultimately restoring the innate antiviral response. These findings strongly suggest that DV-B-120 holds promise as a therapeutic agent against DENV infection and highlight its potential contribution in addressing the current lack of effective treatments for this infectious disease. IMPORTANCE The prevalence of dengue virus (DENV) infection in tropical and subtropical regions is escalating due to factors like climate change and mosquito vector expansion. With over 300 million annual infections and potentially fatal outcomes, the urgent need for effective treatments is evident. While the approved Dengvaxia vaccine has variable efficacy, there are currently no antiviral drugs for DENV. This study explores seven compounds targeting the NS2B-NS3 protease, a crucial protein in DENV replication. These compounds exhibit inhibitory effects on DENV-2 NS2B-NS3, holding promise for disrupting viral replication and preventing severe manifestations. However, further research, including animal testing, is imperative to assess therapeutic efficacy and potential toxicity. Developing safe and potent treatments for DENV infection is critical in addressing the rising global health threat posed by this virus. The prevalence of dengue virus (DENV) infection in tropical and subtropical regions is escalating due to factors like climate change and mosquito vector expansion. With over 300 million annual infections and potentially fatal outcomes, the urgent need for effective treatments is evident. While the approved Dengvaxia vaccine has variable efficacy, there are currently no antiviral drugs for DENV. This study explores seven compounds targeting the NS2B-NS3 protease, a crucial protein in DENV replication. These compounds exhibit inhibitory effects on DENV-2 NS2B-NS3, holding promise for disrupting viral replication and preventing severe manifestations. However, further research, including animal testing, is imperative to assess therapeutic efficacy and potential toxicity. Developing safe and potent treatments for DENV infection is critical in addressing the rising global health threat posed by this virus. |
| 英文关键词 | DV-B-120; selectivity index; competitive inhibitor; NS2B-NS3 protease |
| 语种 | 英语 |
| WOS研究方向 | Virology |
| WOS类目 | Virology |
| WOS记录号 | WOS:001193082400001 |
| 来源期刊 | JOURNAL OF VIROLOGY
 |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/296358 |
| 作者单位 | Kaohsiung Medical University; Kaohsiung Medical University; Kaohsiung Medical University; Kaohsiung Medical University; Chia Nan University of Pharmacy & Science; China Medical University Taiwan; China Medical University Taiwan; Kaohsiung Medical University |
| 推荐引用方式 GB/T 7714 | Huang, Yi-Jung,Cheng, Tian-Lu,Wang, Yen-Tseng,et al. Exploring the therapeutic potential of DV-B-120 as an inhibitor of dengue virus infection[J],2024,98(4). |
| APA | Huang, Yi-Jung.,Cheng, Tian-Lu.,Wang, Yen-Tseng.,Chen, Chien-Shu.,Leu, Yu-Ling.,...&Chuang, Chih-Hung.(2024).Exploring the therapeutic potential of DV-B-120 as an inhibitor of dengue virus infection.JOURNAL OF VIROLOGY,98(4). |
| MLA | Huang, Yi-Jung,et al."Exploring the therapeutic potential of DV-B-120 as an inhibitor of dengue virus infection".JOURNAL OF VIROLOGY 98.4(2024). |
| 条目包含的文件 | 条目无相关文件。 | |||||
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