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关注的新兴 SARS-CoV-2 变体可能会扩大宿主范围至鸡:来自 AXL、NRP1 和 ACE2 受体的见解。

Emerging SARS-CoV-2 variants of concern potentially expand host range to chickens: insights from AXL, NRP1 and ACE2 receptors.

机构信息

Yunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, 650118, Yunnan Province, China.

Kunming Medical University, Kunming, Yunnan, China.

出版信息

Virol J. 2023 Aug 29;20(1):196. doi: 10.1186/s12985-023-02123-x.

Abstract

BACKGROUND

The possibilities of cross-species transmission of SARS-CoV-2 variants of concern (VOCs) between humans and poultry species are unknown. The analysis of the structure of receptor was used to investigate the potential of emerging SARS-CoV-2 VOCs to expand species tropism to chickens based on the interaction between Spike (S) protein and tyrosine kinase receptor UFO (AXL), angiotensin-converting enzyme 2 (ACE2), and neuropilin 1 (NRP1) with substantial public health importance.

METHODS

The structural and genetic alignment and surface potential analysis of the amino acid (aa) in ACE2, AXL, and NRP1 in human, hamster, mouse, mink, ferret, rhesus monkey and chickens were performed by Swiss-Model and pymol software. The critical aa sites that determined the susceptibility of the SARS-CoV-2 to the host were screened by aligning the residues interfacing with the N-terminal domain (NTD) or receptor-binding domain (RBD) of Spike protein.

RESULTS

The binding modes of chickens AXL and ACE2 to S protein are similar to that of the ferret. The spatial structure and electrostatic surface potential of NRP1 showed that SARS-CoV-2 VOCs could not invade chickens through NRP1 easily.

CONCLUSION

These results suggested that emerging SARS-CoV-2 VOCs potentially expand the host range to chickens mainly through ACE2 and AXL receptors, while NRP1 receptor may rarely participate in the future epidemic of coronavirus disease 2019 in chickens.

摘要

背景

目前尚不清楚人类和家禽物种之间 SARS-CoV-2 变体(VOC)的跨物种传播的可能性。通过分析受体的结构,基于 Spike(S)蛋白与酪氨酸激酶受体 UFO(AXL)、血管紧张素转换酶 2(ACE2)和神经纤毛蛋白 1(NRP1)之间的相互作用,研究了新兴 SARS-CoV-2 VOC 扩大物种嗜性以感染鸡的潜力,这对公共卫生具有重要意义。

方法

使用 Swiss-Model 和 pymol 软件对人类、仓鼠、小鼠、水貂、雪貂、恒河猴和鸡的 ACE2、AXL 和 NRP1 中的氨基酸(aa)进行结构和遗传比对及表面电势分析。通过对接 Spike 蛋白的 N 端结构域(NTD)或受体结合结构域(RBD)的界面残基,筛选出决定 SARS-CoV-2 对宿主易感性的关键 aa 位点。

结果

鸡 AXL 和 ACE2 与 S 蛋白的结合模式与雪貂相似。NRP1 的空间结构和静电表面电势表明,SARS-CoV-2 VOC 不易通过 NRP1 入侵鸡。

结论

这些结果表明,新兴的 SARS-CoV-2 VOC 可能主要通过 ACE2 和 AXL 受体扩大宿主范围至鸡,而 NRP1 受体在未来的鸡 2019 年冠状病毒病流行中可能很少参与。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27fb/10466743/ce12370272f3/12985_2023_2123_Fig1_HTML.jpg

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