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Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution.
Nat Commun. 2021 03 11; 12(1):1607.NC

Abstract

In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the "down" conformation, indicating they are more prone to adopt the receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. We further identified critical residues in the RBD underlying different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes. These results collectively indicate that tight RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.

Authors+Show Affiliations

The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084, Beijing, China.The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084, Beijing, China.The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084, Beijing, China.The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084, Beijing, China.Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084, Beijing, China.The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084, Beijing, China.Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084, Beijing, China. xinquanwang@mail.tsinghua.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33707453

Citation

Zhang, Shuyuan, et al. "Bat and Pangolin Coronavirus Spike Glycoprotein Structures Provide Insights Into SARS-CoV-2 Evolution." Nature Communications, vol. 12, no. 1, 2021, p. 1607.
Zhang S, Qiao S, Yu J, et al. Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution. Nat Commun. 2021;12(1):1607.
Zhang, S., Qiao, S., Yu, J., Zeng, J., Shan, S., Tian, L., Lan, J., Zhang, L., & Wang, X. (2021). Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution. Nature Communications, 12(1), 1607. https://doi.org/10.1038/s41467-021-21767-3
Zhang S, et al. Bat and Pangolin Coronavirus Spike Glycoprotein Structures Provide Insights Into SARS-CoV-2 Evolution. Nat Commun. 2021 03 11;12(1):1607. PubMed PMID: 33707453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution. AU - Zhang,Shuyuan, AU - Qiao,Shuyuan, AU - Yu,Jinfang, AU - Zeng,Jianwei, AU - Shan,Sisi, AU - Tian,Long, AU - Lan,Jun, AU - Zhang,Linqi, AU - Wang,Xinquan, Y1 - 2021/03/11/ PY - 2020/09/17/received PY - 2021/02/11/accepted PY - 2021/3/12/entrez PY - 2021/3/13/pubmed PY - 2021/3/23/medline SP - 1607 EP - 1607 JF - Nature communications JO - Nat Commun VL - 12 IS - 1 N2 - In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the "down" conformation, indicating they are more prone to adopt the receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. We further identified critical residues in the RBD underlying different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes. These results collectively indicate that tight RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/33707453/Bat_and_pangolin_coronavirus_spike_glycoprotein_structures_provide_insights_into_SARS_CoV_2_evolution_ L2 - https://doi.org/10.1038/s41467-021-21767-3 DB - PRIME DP - Unbound Medicine ER -