ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicA Nanoparticle-Antibody Alliance: A New Era in Disease DiagnosticsView all 3 articles
A trans-activating transduction peptide fused nanobody targeting viral nonstructural protein NS4B inhibits bovine viral diarrhea virus (BVDV) replication
Provisionally accepted
- Northwest A&F University, Xianyang, China
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Bovine viral diarrhea virus (BVDV) is a major threat to cattle worldwide. Nanobodies (Nbs), with their small size, high specificity, and affinity, are promising therapeutics. However, their application against intracellular pathogens is limited by poor cell membrane impermeability. In this study, a nanobody Nb91 targeting the BVDV nonstructural protein NS4B was isolated. Intracellular expressed Nb91 was shown to markedly suppress BVDV replication in MDBK cells (approximately 100%). Then, the Nb91 fused with the trans-activating transduction (TAT) peptide (TAT-Nb91) was developed and used to determine its effect on BVDV replication. Our results demonstrated that TAT mediated the internalization of Nb91 in a dose-and time-dependent manner. The inhibition rate of TAT-Nb91 against both cytopathogenic (CP) and noncytopathogenic (NCP) biotypes of BVDV in MDBK cells could reach 70% and 40%, respectively. Furthermore, TAT-Nb91 can also inhibit both biotypes BVDV replication (>50%) in Bend cells, the primary targets of BVDV infection in vivo. Epitope mapping showed that the NS4Baa328-347 was the key amino acid binding to TAT-Nb91. Collectively, these findings establish TAT-fused nanobodies targeting the conserved NS4B protein as a promising new therapeutic strategy against BVDV.
Keywords: BVDV, NS4B, Nanobody, at, Antiviral Agents
Received: 25 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Zhao, Lv, Wenqi, Zhang, Wei, Fang, Huang, Chen, Wang and Qi. 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: Xuefeng Qi, yxyan2002@163.com
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