Chen Rui, Zhou Guiping, Yang Junpeng, Yuan Rong, Sun Ying, Liang Yixiao, Wu Rui, Wen Yiping, Wang Yiping, Zhao Qin, Du Senyan, Yan Qigui, Cao Sanjie, Huang Xiaobo
Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Chengdu Livestock and Poultry Genetic Resources Protection Center, Chengdu, China.
J Virol. 2025 Feb 25;99(2):e0202524. doi: 10.1128/jvi.02025-24. Epub 2025 Jan 22.
Porcine deltacoronavirus (PDCoV) is an enteric pathogen that burdens the global pig industry and is a public health concern. The development of effective antiviral therapies is necessary for the prevention and control of PDCoV, yet to date, there are few studies on the therapeutic potential of PDCoV-neutralizing antibodies. Here, we investigate the therapeutic potential of a novel monoclonal antibody (mAb 4A6) which targets the PDCoV S1 protein and effectively neutralizes PDCoV, both pre- and post-attachment on cells, with IC50 values of 0.537 and 8.487 µg/mL, respectively. A phage-display peptide library was used to determine the epitope recognized by mAb 4A6, and two mimotopes, QYPVSYA (P1) and FPHWPTI (P2), were identified. KLH-P1 reacted with PDCoV-positive sera but failed to induce PDCoV-specific IgG and neutralizing antibodies in mice, suggesting P1 does not fully mimic the conformational epitope. Molecular docking and alanine scanning mutagenesis revealed that S461, P462, T463, E465, and Y467 on the S protein are essential for mAb 4A6 binding. Antibody therapy experiments in PDCoV-infected piglets showed that administering mAb 4A6 once or twice could delay the onset of diarrhea symptoms, reduce the severity of diarrhea, and decrease virus shedding. Taken together, our findings demonstrate that mAb 4A6 holds promise as a treatment against PDCoV, and the amino acids recognized by mAb 4A6 will be valuable for developing novel epitope-based vaccines or antiviral drugs.
Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that poses a potential threat to public health. Developing effective antiviral therapies is crucial for its prevention and control. Here, we demonstrated that mAb 4A6 shows promise as a treatment against PDCoV. Antibody therapy experiments conducted on PDCoV-infected piglets revealed that administering mAb 4A6 once or twice could delay the onset of diarrhea symptoms, reduce the severity of diarrhea, and decrease virus shedding. Furthermore, we characterized the conformational epitope (S461, P462, T463, E465, and Y467) recognized by mAb 4A6 through an integrated approach involving phage display peptide library, molecular docking, and alanine scanning mutagenesis. More importantly, mAb 4A6 exhibits a broad-spectrum neutralizing activity against different PDCoV strains. These findings indicate that mAb 4A6 has promising therapeutic value for PDCoV-infected piglets, and the identification of mAb 4A6 recognized epitope may provide a new idea for the identification of conformational epitopes.
猪德尔塔冠状病毒（PDCoV）是一种肠道病原体，给全球养猪业带来负担，也是一个公共卫生问题。开发有效的抗病毒疗法对于预防和控制PDCoV至关重要，但迄今为止，关于PDCoV中和抗体治疗潜力的研究很少。在这里，我们研究了一种新型单克隆抗体（mAb 4A6）的治疗潜力，该抗体靶向PDCoV S1蛋白，可有效中和PDCoV，在细胞附着前和附着后均能发挥作用，IC50值分别为0.537和8.487 µg/mL。利用噬菌体展示肽库确定mAb 4A6识别的表位，鉴定出两个模拟表位，即QYPVSYA（P1）和FPHWPTI（P2）。KLH-P1与PDCoV阳性血清发生反应，但未能在小鼠中诱导出PDCoV特异性IgG和中和抗体，这表明P1不能完全模拟构象表位。分子对接和丙氨酸扫描诱变显示，S蛋白上的S461、P462、T463、E465和Y467对于mAb 4A6的结合至关重要。在感染PDCoV的仔猪中进行的抗体治疗实验表明，单次或两次给予mAb 4A6可延迟腹泻症状的出现，减轻腹泻的严重程度，并减少病毒脱落。综上所述，我们的研究结果表明mAb 4A6有望成为治疗PDCoV的药物，mAb 4A6识别的氨基酸对于开发新型基于表位的疫苗或抗病毒药物具有重要价值。
猪德尔塔冠状病毒（PDCoV）是一种新型猪肠道致病性冠状病毒，对公共卫生构成潜在威胁。开发有效的抗病毒疗法对其预防和控制至关重要。在这里，我们证明mAb 4A6有望成为治疗PDCoV的药物。在感染PDCoV的仔猪上进行的抗体治疗实验表明，单次或两次给予mAb 4A6可延迟腹泻症状的出现，减轻腹泻的严重程度，并减少病毒脱落。此外，我们通过噬菌体展示肽库、分子对接和丙氨酸扫描诱变等综合方法，对mAb 4A6识别的构象表位（S461、P462、T463、E465和Y467）进行了表征。更重要的是，mAb 4A6对不同的PDCoV毒株表现出广谱中和活性。这些发现表明mAb 4A6对感染PDCoV的仔猪具有有前景的治疗价值，mAb 4A6识别表位的鉴定可能为构象表位的鉴定提供新思路。
