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壳聚糖修饰的 AgNPs 通过靶向刺突蛋白有效抑制猪冠状病毒诱导的宿主细胞感染。

Chitosan-Modified AgNPs Efficiently Inhibit Swine Coronavirus-Induced Host Cell Infections via Targeting the Spike Protein.

机构信息

College of Biology, Hunan University, Changsha 410082, China.

Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.

出版信息

Biomolecules. 2024 Sep 13;14(9):1152. doi: 10.3390/biom14091152.

Abstract

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has filled a gap in our knowledge regarding the prevention of CoVs. Swine coronavirus (CoV) is a significant pathogen that causes huge economic losses to the global swine industry. Until now, anti-CoV prevention and control have been challenging due to the rapidly generated variants. Silver nanoparticles (AgNPs) with excellent antimicrobial activity have attracted great interest for biosafety prevention and control applications. In this study, we synthesized chitosan-modified AgNPs (Chi-AgNPs) with good biocompatibility to investigate their antiviral effects on swine CoVs. In vitro assays showed that Chi-AgNPs could significantly impaired viral entry. The direct interaction between Chi-AgNPs and CoVs can destroy the viral surface spike (S) protein secondary structure associated with viral membrane fusion, which is caused by the cleavage of disulfide bonds in the S protein. Moreover, the mechanism showed that Chi-AgNPs reduced the virus-induced apoptosis of Vero cells via the ROS/p53 signaling activation pathway. Our data suggest that Chi-AgNPs can serve as a preventive strategy for CoVs infection and provide a molecular basis for the viricidal effect of Chi-AgNPs on CoVs.

摘要

新型冠状病毒肺炎(COVID-19)由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起,填补了我们对冠状病毒预防知识的空白。猪冠状病毒(CoV)是一种重要的病原体,给全球养猪业造成了巨大的经济损失。到目前为止,由于不断产生的变异,抗 CoV 的防控一直具有挑战性。具有优异抗菌活性的银纳米粒子(AgNPs)因其在生物安全防控方面的应用而受到极大关注。在这项研究中,我们合成了具有良好生物相容性的壳聚糖修饰的 AgNPs(Chi-AgNPs),以研究其对猪 CoV 的抗病毒作用。体外实验表明,Chi-AgNPs 可显著抑制病毒进入。Chi-AgNPs 与 CoVs 的直接相互作用可以破坏与病毒膜融合相关的病毒表面刺突(S)蛋白二级结构,这是由 S 蛋白中二硫键的裂解引起的。此外,该机制表明 Chi-AgNPs 通过 ROS/p53 信号激活途径降低了病毒诱导的 Vero 细胞凋亡。我们的数据表明,Chi-AgNPs 可作为预防 CoVs 感染的策略,并为 Chi-AgNPs 对 CoVs 的杀菌作用提供了分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7fb/11430280/2cf36da4bba2/biomolecules-14-01152-sch001.jpg

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