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分析血管紧张素转换酶2(ACE2)直系同源物以预测对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)高度易感的动物宿主范围。

analysis of ACE2 orthologues to predict animal host range with high susceptibility to SARS-CoV-2.

作者信息

Bouricha El Mehdi, Hakmi Mohammed, Akachar Jihane, Belyamani Lahcen, Ibrahimi Azeddine

机构信息

Medical Biotechnology Laboratory (MedBiotech), Rabat Medical and Pharmacy School, Mohammed Vth University in Rabat, Rabat, Morocco.

Emergency Department, Military Hospital Mohammed V, Rabat Medical and Pharmacy School, Mohammed Vth University in Rabat, Rabat, Morocco.

出版信息

3 Biotech. 2020 Nov;10(11):483. doi: 10.1007/s13205-020-02471-3. Epub 2020 Oct 21.

DOI:10.1007/s13205-020-02471-3
PMID:33101829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7577366/
Abstract

SARS-CoV-2, which causes severe pneumonia epidemics, probably originated from Chinese horseshoe bats, but the intermediate and host range is still unknown. ACE2 is the entry receptor for SARS-CoV-2. The binding capacity of SARS-CoV-2 spike protein to ACE2 is the critical determinant of viral host range and cross-species infection. Here, we used an approach to predict the potential animals range with high susceptibility to SARS-CoV-2 by modelling and studying the Spike-ACE2 interaction of 22 domestic and wild animals. Our results showed that all studied animals are potentially susceptible to SARS-CoV-2 infection with a slight difference in the binding affinity and stability of their ACE2-RBD complexes. Furthermore, we identified a specific substitution of tyrosine to histidine at position 41 in ACE2 that likely reduces the affinity to SARS-CoV-2 in horses and greater horseshoe bats. These results may help to provide important insights into SARS-CoV-2 host range which will make it possible to control the spread of the virus and identify animal models that could be used for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

摘要

导致严重肺炎疫情的新冠病毒(SARS-CoV-2)可能起源于中华菊头蝠,但中间宿主和宿主范围仍不清楚。血管紧张素转换酶2(ACE2)是新冠病毒的进入受体。新冠病毒刺突蛋白与ACE2的结合能力是病毒宿主范围和跨物种感染的关键决定因素。在此,我们通过建模和研究22种家养和野生动物的刺突蛋白-ACE2相互作用,采用一种方法预测对新冠病毒具有高易感性的潜在动物范围。我们的结果表明,所有研究的动物都可能易受新冠病毒感染,其ACE2-RBD复合物的结合亲和力和稳定性略有差异。此外,我们在ACE2的第41位发现了酪氨酸到组氨酸的特定替换,这可能会降低马和大菊头蝠对新冠病毒的亲和力。这些结果可能有助于为新冠病毒的宿主范围提供重要见解,这将有助于控制病毒传播,并确定可用于筛选抗新冠病毒抗病毒药物或候选疫苗的动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0531/7578211/8035c2d41ccf/13205_2020_2471_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0531/7578211/d6f094c68c88/13205_2020_2471_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0531/7578211/1674c959a94c/13205_2020_2471_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0531/7578211/8035c2d41ccf/13205_2020_2471_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0531/7578211/d6f094c68c88/13205_2020_2471_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0531/7578211/1674c959a94c/13205_2020_2471_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0531/7578211/8035c2d41ccf/13205_2020_2471_Fig3_HTML.jpg

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