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比较 ACE2 变异与灵长类动物 COVID-19 风险。

Comparative ACE2 variation and primate COVID-19 risk.

机构信息

Department of Anthropology and Archaeology, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada.

Department of Medical Genetics, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada.

出版信息

Commun Biol. 2020 Oct 27;3(1):641. doi: 10.1038/s42003-020-01370-w.

Abstract

The emergence of SARS-CoV-2 has caused over a million human deaths and massive global disruption. The viral infection may also represent a threat to our closest living relatives, nonhuman primates. The contact surface of the host cell receptor, ACE2, displays amino acid residues that are critical for virus recognition, and variations at these critical residues modulate infection susceptibility. Infection studies have shown that some primate species develop COVID-19-like symptoms; however, the susceptibility of most primates is unknown. Here, we show that all apes and African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2. Monkeys in the Americas, and some tarsiers, lemurs and lorisoids, differ at critical contact residues, and protein modeling predicts that these differences should greatly reduce SARS-CoV-2 binding affinity. Other lemurs are predicted to be closer to catarrhines in their susceptibility. Our study suggests that apes and African and Asian monkeys, and some lemurs, are likely to be highly susceptible to SARS-CoV-2. Urgent actions have been undertaken to limit the exposure of great apes to humans, and similar efforts may be necessary for many other primate species.

摘要

SARS-CoV-2 的出现导致了超过一百万人死亡和全球大规模混乱。这种病毒感染也可能对我们最亲近的生物——灵长类动物构成威胁。宿主细胞受体 ACE2 的接触表面显示出对病毒识别至关重要的氨基酸残基,而这些关键残基的变异调节感染易感性。感染研究表明,一些灵长类动物出现了类似 COVID-19 的症状;然而,大多数灵长类动物的易感性尚不清楚。在这里,我们表明所有的猿类和非洲和亚洲的猴子(包括旧大陆猴)都表现出与人类 ACE2 相同的 12 个关键氨基酸残基。美洲的猴子以及一些眼镜猴、狐猴和懒猴类,在关键接触残基上存在差异,蛋白模型预测这些差异应该大大降低 SARS-CoV-2 的结合亲和力。其他的狐猴在易感性上更接近旧大陆猴。我们的研究表明,猿类、非洲和亚洲的猴子以及一些狐猴很可能对 SARS-CoV-2 高度易感。已经采取了紧急行动来限制大猩猩与人类的接触,对于许多其他灵长类动物来说,可能也需要采取类似的措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcf9/7591510/301d4b1f3c25/42003_2020_1370_Fig1_HTML.jpg

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