ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1651730
c-Met Inhibitor NVP-BVU972 Induces Antiviral Protection and Suppresses NF-κB-Mediated Inflammation
Provisionally accepted
Yang Zhao*
Yunfei Xie
Xingyu Chen
Hongli JiaXiao Wang
Tianyi Liu
Haocheng WangYang li*
Xuefei Guo*fuping you*- Peking University, Beijing, China
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Inhibiting viral replication and limiting NF-κB-driven inflammation simultaneously is essential for better antiviral therapy, highlighting the urgent need for a single agent that achieves both functions. Here, we reported NVP-BVU972 (NVP), a selective c-Met inhibitor, induced a robust antiviral state and inhibited NF-κB-mediated inflammation. The dual functions blocked replication of diverse RNA viruses (VSV, EMCV, MHV) and DNA viruses (HSV-1, VACV) and reduced systemic cytokine levels (Il1β, Il6, Tnfα) in vitro and in vivo. Mechanistically, NVP reprogrammed inflammation-related loci by modulating both gene expression and chromatin accessibility. In addition, inhibition of H3K9 methylation by chaetocin reversed NVP's antiviral activity. These findings unveil NVP as a promising host-directed agent that simultaneously limits viral propagation and reduces inflammation, and suggest repurposing NVP as a broad-spectrum antiviral.
Keywords: NVP-BVU972, C-Met inhibitor, Broad-spectrum antiviral, NF-κB-mediated inflammation, epigenetic reprogramming
Received: 22 Jun 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Zhao, Xie, Chen, Jia, Wang, Liu, Wang, li, Guo and you. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yang Zhao, Peking University, Beijing, China
Yang li, Peking University, Beijing, China
Xuefei Guo, Peking University, Beijing, China
fuping you, Peking University, Beijing, China
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