Screening and Characterization of TAT-Fused Nanobodies Targeting Bovine Viral Diarrhea Virus NS3/NS5A for Antiviral Application

TL;DR

Researchers developed a nanobody fused with a cell-penetrating peptide to target a key protein in bovine viral diarrhea virus, showing potential as an antiviral treatment.

Contribution

A novel TAT-fused nanobody targeting BVDV NS5A was developed and shown to inhibit viral replication in bovine cells.

Findings

Nb7 nanobody specifically targets BVDV NS5A protein.

TAT-Nb7 effectively enters MDBK cells and inhibits viral replication.

TAT-Nb7 shows promise as a therapeutic candidate for BVDV.

Abstract

Bovine viral diarrhea virus (BVDV) is a major pathogen responsible for significant economic losses in the global cattle industry. The diverse transmission routes and the characteristics of asymptomatic infections make it difficult to contain the spread; there is an urgent need to develop new effective antiviral strategies. Nanobodies (Nbs) have become a promising new type of antiviral agent due to their advantages, including small molecular size, stable structure, high specificity, and ease of production. This study successfully screened a specific nanobody, Nb7, targeting the key functional protein NS5A of BVDV using phage display technology. Furthermore, the nanobody was effectively delivered into Madin–Darby bovine kidney (MDBK) cells by fusing it with the cell-penetrating peptide TAT. The results demonstrate that TAT-Nb7, specifically targeting the non-structural protein NS5A of BVDV, significantly inhibits viral replication in MDBK cells. In conclusion, this study indicates that TAT-Nb7 holds promise as a therapeutic candidate for the prevention and control of BVDV infection.

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