Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion

Benton, D.J.; Wrobel, Antoni G.; Xu, Pengqi; Roustan, Chloë; Martin, Stephen R.; Rosenthal, Peter B.; Skehel, J.J.; Gamblin, S.J.

doi:10.1038/s41586-020-2772-0

Cited by 804 publications

(1,073 citation statements)

References 51 publications

(91 reference statements)

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“…These studies suggest that the release of the S1 by receptor or antibody binding is a precondition for coronavirus fusion. Similar observations were also reported for SARS-CoV-2 [61]. Spikes in a post-fusion-like state were observed on the surface of SARS-CoV-2 with electron microscopy [43,44].…”

Section: Conformational Changes Of the Spike Proteins During Virus Entrysupporting

confidence: 85%

“…Binding of ACE2 to one SARS-CoV RBD opens up the RBD (the ACE2-bound RBD has an "up" angle of 51-111 degree compared to 52-70 degrees for the uncomplexed RBD) and induces the release of the S1 subunits from the spikes and the pre-to post-fusion conformation transition of the spike [25]. A two-RBD "up" state and a three-RBD "up" state were observed after ACE2 binding to the S of SARS-CoV-2 [61]. These states are not stable and are prone to switch to the post-fusion state.…”

Section: High-affinity Binding To the Ace2 Receptormentioning

confidence: 99%

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Spike Glycoprotein-Mediated Entry of SARS Coronaviruses

Wang

Xiang

2020

Viruses

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Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 are enveloped, positive-sense, single-stranded RNA viruses and causes of epidemic diseases that have resulted in public health emergencies worldwide. Angiotensin-converting enzyme 2 (ACE2) is the receptor that allows the entry of these two viruses into host cells, a key step in the life cycle of the pathogens. The characterization of the interactions of ACE2 with the viral spike glycoproteins and structural studies of the ACE2-binding-induced conformational changes in the viral spike glycoproteins have furthered our understanding of the entry processes of these two viruses, and these studies provide useful information that will facilitate the development of antiviral agents and vaccines to control the diseases.

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Section: Conformational Changes Of the Spike Proteins During Virus Entrysupporting

confidence: 85%

Section: High-affinity Binding To the Ace2 Receptormentioning

confidence: 99%

Spike Glycoprotein-Mediated Entry of SARS Coronaviruses

Wang

Xiang

2020

Viruses

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“…Complex structural determinations have revealed the interactions between SARS-CoV-2 RBD and hACE2 at an atomic level 13-16 . Cryo-EM studies revealed that the SARS-CoV-2 S trimer, similar to that of SARS-CoV, needs to have at least one RBD in an “up” conformation to bind hACE2 17-23 . Therefore, a spike trimer with all three RBDs “down” is in a receptor-binding inactive state, and the conformational change of at least one RBD from “down” to “up” switches the spike trimer to a receptor-binding active state 18 .…”

Section: Introductionmentioning

confidence: 99%

Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution

Zhang

Qiao

et al. 2020

Preprint

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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 this 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. Through structure and sequence comparisons, we identified critical residues in the RBD that underlie the different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes and propose that N-linked glycans serve as conformational control elements of the RBD. These results collectively indicate that strong RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.

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“…Анализ S-белков последних (по времени возникновения) штаммов из европейских стран и Китая, для которых в базе данных приводятся сведения по секвенированному геному, свидетельствуют о том, что все они содержат мутацию D614G. Ее возникновение снижает отрицательную полярность S1-субъединицы S-белка и соответственно увеличивает электростатическое взаимодействие S-белка с клеточными рецепторами коронавируса SARS-Cov-2 (ангиотензин-конвертирующим энзимом-2 и нейропилином-1, имеющими выраженную отрицательную полярность) [36], а также придает большую конформационную гибкость молекуле S-белка [37].…”

Section: проблемные статьиunclassified

Vaccines against Covid-19: the Comparative Estimates of Risks in Adenovirus Vectors

Kharchenko

2020

Epidemiology and Vaccinal Prevention

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Relevance. The vaccine against the SARS-Cov-2 coronavirus is considered as the most promising approach to curb (tame) a current pandemic and prevent new one. Three vaccines (AstraZeneca’s СhAdOx1 nCov-19, CanSino’s vaccine and Russia’s Sputnik V one) are in Phase III clinical trials and have the S protein as immunogen but different adenovirus vectors. It is known adverse neurological events associated with the СhAdOx1 nCov-19 vacсine.Aim is to investigate the distribution of homologous sequences of adenovirus proteins in human nervous and immune systems proteins, estimate potential risks of using adenovirus vectors in vaccines and discuss possible mechanisms inducing immune damage in the nervous system.Materials and methods. For the computer analysis of peptide (immune epitope) relationship between adenovirus structural proteins and human proteins, the search of homologous sequences was made. All protein sequences were used from databases available on the INTERNET.Results. Among adenoviruses (НАд5, НАд26 , ChАдY25, and SAd3) ChАдY25 has the highest content of sequences homologous to human nervous system proteins that may be the cause of autoimmune complications in vaccination.Conclusion: In AstraZeneca’s СhAdOx1 nCov-19 vaccine there are a large number of peptide sequences homologous to human nervous system proteins and it allows to predict the possible risks with this vaccine.

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Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion

Cited by 804 publications

References 51 publications

Spike Glycoprotein-Mediated Entry of SARS Coronaviruses

Spike Glycoprotein-Mediated Entry of SARS Coronaviruses

Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution

Vaccines against Covid-19: the Comparative Estimates of Risks in Adenovirus Vectors

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