The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins.
The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins.
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DOI：
10.1371/journal.pbio.3001016
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发表时间：
2020-12
期刊：
影响因子：
9.8
通讯作者：
Bailey D
中科院分区：
文献类型：
--
作者：
Conceicao C;Thakur N;Human S;Kelly JT;Logan L;Bialy D;Bhat S;Stevenson-Leggett P;Zagrajek AK;Hollinghurst P;Varga M;Tsirigoti C;Tully M;Chiu C;Moffat K;Silesian AP;Hammond JA;Maier HJ;Bickerton E;Shelton H;Dietrich I;Graham SC;Bailey D
SARS冠状病毒2（SARS-CoV-2）于2019年底出现，导致2019冠状病毒病（COVID-19）大流行，继续导致全球人口的重大死亡。鉴于其序列与SARS-CoV以及在蝙蝠中传播的相关冠状病毒相似，SARS-CoV-2被认为起源于中国的翼手目物种。然而，目前尚不清楚该病毒是直接传播给人类还是通过中间宿主传播，也不清楚该病毒感染伴侣动物、牲畜和野生动物的可能性。使用替代品进入试验和活病毒的组合，我们证明，除了人血管紧张素转换酶2（ACE2），刺突糖蛋白的SARS-CoV-2有一个广泛的宿主嗜性哺乳动物ACE2受体，尽管分歧的氨基酸刺突受体结合位点上的这些蛋白质。在我们研究的22种不同的宿主中，来自狗、猫和牛的ACE2蛋白对SARS-CoV-2最具容许性，而蝙蝠和鸟类的ACE2蛋白是使用效率最低的受体。我们研究的3种遗传上不同的蝙蝠ACE2蛋白中任何一种都没有显著的向性，这表明SARS-CoV-2受体的使用可能在从蝙蝠到人的人畜共患传播过程中发生了转移，可能是在中间水库中。将SARS-CoV-2受体与相关冠状病毒SARS-CoV和RaTG13的使用进行比较，发现了不同的嗜性，其中2种人类病毒更接近。最后，利用生物信息学、结构数据和靶向诱变，我们鉴定了Spike-ACE2界面内的氨基酸残基，这可能在人类SARS-CoV-2的出现中发挥了关键作用。SARS-CoV-2在病毒进入点的明显广泛嗜性证实了对广泛的伴侣动物、牲畜和野生动物的潜在感染风险。一项使用替代进入试验和活病毒相结合的研究表明，SARS-CoV-2可能具有广泛的宿主范围，揭示了病毒的刺突蛋白可以使用广泛的宿主ACE2受体进入细胞，并且这种蛋白质的序列可能在人畜共患病跳跃到人类的过程中发生了变化。
SARS Coronavirus 2 (SARS-CoV-2) emerged in late 2019, leading to the Coronavirus Disease 2019 (COVID-19) pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock, and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus, we demonstrate that, in addition to human angiotensin-converting enzyme 2 (ACE2), the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the 22 different hosts we investigated, ACE2 proteins from dog, cat, and cattle were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the 3 genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Comparison of SARS-CoV-2 receptor usage to the related coronaviruses SARS-CoV and RaTG13 identified distinct tropisms, with the 2 human viruses being more closely aligned. Finally, using bioinformatics, structural data, and targeted mutagenesis, we identified amino acid residues within the Spike–ACE2 interface, which may have played a pivotal role in the emergence of SARS-CoV-2 in humans. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock, and wildlife. A study using a combination of surrogate entry assays and live virus suggests that SARS-CoV-2 may have a broad host-range, revealing that the virus's spike protein can use a broad range of host ACE2 receptors to enter cells and that the sequence of this protein might have changed during the zoonotic jump into humans.
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影响因子：
5.4
作者：
Li Y;Wang H;Tang X;Fang S;Ma D;Du C;Wang Y;Pan H;Yao W;Zhang R;Zou X;Zheng J;Xu L;Farzan M;Zhong G
通讯作者：
Zhong G
DOI：
10.1073/pnas.0712051105
发表时间：
2008-03-25
影响因子：
11.1
作者：
Li, Nainong;Zhao, Dongchang;Zeng, Defu
通讯作者：
Zeng, Defu
影响因子：
10.7
作者：
Kumar, Sudhir;Stecher, Glen;Tamura, Koichiro
通讯作者：
Tamura, Koichiro
影响因子：
30.3
作者：
Kim, Young-Il;Kim, Seong-Gyu;Choi, Young Ki
通讯作者：
Choi, Young Ki
影响因子：
64.8
作者：
Dinnon KH 3rd;Leist SR;Schäfer A;Edwards CE;Martinez DR;Montgomery SA;West A;Yount BL Jr;Hou YJ;Adams LE;Gully KL;Brown AJ;Huang E;Bryant MD;Choong IC;Glenn JS;Gralinski LE;Sheahan TP;Baric RS
通讯作者：
Baric RS