Vascular endothelial growth factor receptor 2 as a potential host target for the inhibition of enterovirus replication
As the first clinical case was identified in the United States, EV-A71, a significant neurotropic enterovirus, has been a common cause of hand, foot, and mouth disease (HFMD) in infants and young children. Developing an effective antiviral agent for EV-A71 and other human enteroviruses is crucial, as these viral pathogens consistently cause outbreaks in humans. In this study, we demonstrated that multiple inhibitors against VEGFRs effectively reduced EV-A71 replication, with Pazopanib emerging as the top candidate. Furthermore, Pazopanib also attenuated the replication of other enteroviruses, including CVA10, CVB1, EV-D70, and HRV-A, displaying broad-spectrum anti-enterovirus activity. Given that Pazopanib targets various VEGFRs, we narrowed the focus to VEGFR2 using knockdown and overexpression experiments. Transcriptomic analysis suggests that Pazopanib's potential downstream targets involve the TSAd-Src-PI3K-Akt pathway. Our work may contribute to identifying targets for antiviral inhibitors and advancing treatments for human enterovirus infections.
Authors
- Longfa Xu (ORCID: https://orcid.org/0000-0001-6307-5665)
- Yinying Lu
- Jincun Zhao (ORCID: https://orcid.org/0000-0003-2515-5589)
- Wenhong Zhang (ORCID: https://orcid.org/0000-0002-9165-3212)
- Rui Qiao (ORCID: https://orcid.org/0000-0003-0210-2863)
- Xiaoyu Zhao (ORCID: https://orcid.org/0000-0002-0347-9104)
- Pengfei Wang (ORCID: https://orcid.org/0000-0003-2454-7652)
- Yi Li (ORCID: https://orcid.org/0000-0002-6439-4294)
- Jing Wu
- Jiayan Li (ORCID: https://orcid.org/0009-0000-3436-0483)
- Meng Hao
- Dong Wang (ORCID: https://orcid.org/0009-0001-8218-3853)
- Tong Cheng (ORCID: https://orcid.org/0000-0002-1638-6214)
Institutions
- Xiamen University (CN)
- Fudan University (CN)
- Southern University of Science and Technology (CN)
- ShanghaiTech University (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN)
- Pudong Medical Center (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Huashan Hospital (CN)
- Shenzhen Third People’s Hospital (CN)
- State Key Laboratory of Genetic Engineering
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Journal of Virology
- Published
- 2024-09-17
- DOI
- https://doi.org/10.1128/jvi.01129-24
- Citations
- 4
- Primary Topic
- Viral Infections and Immunology Research
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Fudan University
- State Key Laboratory of Genetic Engineering
- Shanghai Rising-Star Program
- National Key Research and Development Program of China