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通过抑制nsp13解旋酶将万古霉素重新用作抗猪流行性腹泻病毒的潜在抗病毒药物。

Repurposing Vancomycin as a Potential Antiviral Agent Against PEDV via nsp13 Helicase Inhibition.

作者信息

Chen Qiao, Yu Mengqi, Guo Jiajing, Qiu Jingqi, Liu Fei, Shan Yanke

机构信息

Joint International Research Laboratory of Animal Health and Food Safety of Ministry of Education, Nanjing Agricultural University, Nanjing 210095, China.

Single Molecule Biochemistry & Biomedicine Laboratory (Sinmolab), Nanjing Agricultural University, Nanjing 210095, China.

出版信息

Animals (Basel). 2025 Mar 23;15(7):923. doi: 10.3390/ani15070923.

Abstract

Porcine epidemic diarrhea virus (PEDV) causes a highly contagious intestinal disease with severe economic impacts on the global swine industry. The non-structural protein 13 (nsp13), a viral helicase, is essential for viral replication, making it a promising target for antiviral drug development. In this study, through virtual screening and molecular dynamics simulations, Vancomycin, a small-molecule drug also clinically used as an antibacterial agent, was identified to exhibit a stable binding affinity for PEDV nsp13. The NTPase and ATP-dependent RNA helicase activities of PEDV nsp13 were confirmed , and the optimal biochemical reaction conditions for its dsRNA unwinding activity were established. Further experiments demonstrated that Vancomycin effectively inhibited the dual enzymatic activities of PEDV nsp13 and reduced PEDV infections . This research highlights Vancomycin as a novel inhibitor of PEDV nsp13, providing valuable mechanistic insights and serving as a model for antiviral drug discovery. While this study suggests its potential for repurposing as a therapeutic agent against PEDV, further investigations are required to evaluate its feasibility , particularly in terms of safety, efficacy, and practical applicability.

摘要

猪流行性腹泻病毒(PEDV)引发一种高度传染性的肠道疾病,对全球养猪业造成严重经济影响。非结构蛋白13(nsp13)作为一种病毒解旋酶,对病毒复制至关重要,使其成为抗病毒药物开发的一个有前景的靶点。在本研究中,通过虚拟筛选和分子动力学模拟,确定了临床上也用作抗菌剂的小分子药物万古霉素对PEDV nsp13具有稳定的结合亲和力。证实了PEDV nsp13的NTPase和ATP依赖性RNA解旋酶活性,并确定了其双链RNA解旋活性的最佳生化反应条件。进一步的实验表明,万古霉素有效抑制PEDV nsp13的双重酶活性并减少PEDV感染。本研究突出了万古霉素作为PEDV nsp13的新型抑制剂,提供了有价值的机制见解,并作为抗病毒药物发现的一个模型。虽然本研究表明其有作为抗PEDV治疗剂重新利用的潜力,但需要进一步研究以评估其可行性,特别是在安全性、有效性和实际适用性方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c5/11987754/0a7a275fe046/animals-15-00923-g001.jpg

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