Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola M.; Graham, Barney S.; McLellan, Jason S.

doi:10.1101/2020.02.11.944462

Cited by 1,351 publications

(2,021 citation statements)

References 38 publications

Supporting

Mentioning

1,910

Contrasting

Unclassified

Order By: Relevance

“…Five out of the six critical amino acid (AA) residues in RBD were different between SARS-CoV-2 and SARS-CoV ( Fig. 1B), and a 3D structural analysis indicated that the spike of SARS-CoV-2 has a higher binding affinity to ACE2 than SARS-CoV [23]. Intriguingly, these same six critical AAs are identical between GD Pangolin-CoV and SARS-CoV-2 [16].…”

Section: Molecular Phylogeny and Divergence Between Sars-cov-2 And Rementioning

confidence: 97%

See 1 more Smart Citation

On the origin and continuing evolution of SARS-CoV-2

Tang

et al. 2020

National Science Review

1,562

1,622

View full text Add to dashboard Cite

The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses.Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination.Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (~70%) is more prevalent than the S type (~30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 .

show abstract

Section: Molecular Phylogeny and Divergence Between Sars-cov-2 And Rementioning

confidence: 97%

“…Both SARS-CoV and SARS-CoV-2 bind to ACE2 through the RBD of spike protein in order to initiate membrane fusion and enter human cells [1,2,[22][23][24][25][26]. Five out of the six critical amino acid (AA) residues in RBD were different between SARS-CoV-2 and SARS-CoV ( Fig.…”

Section: Molecular Phylogeny and Divergence Between Sars-cov-2 And Rementioning

confidence: 99%

On the origin and continuing evolution of SARS-CoV-2

Tang

et al. 2020

National Science Review

1,562

1,622

View full text Add to dashboard Cite

show abstract

“…S residues 313-532 were clearly interpretable from the electron density map, with a dual conformation of a loop containing residues 484 to 487 clearly visible in the electron density map (Figure 1). Structure comparison of the unliganded RBD structure presented here, with the stabilized prefusion SARS-CoV-2 Spike (S-2P) molecule structure determined by Cryo-EM (PDB ID: 6VSB) (Wrapp et al, 2020) shows high structural similarity, with an RMSD of 0.68, 0.68, and 0.71 for each of the spike protomers. In the structure of the S-2P molecule (S-2P) (Wrapp et al, 2020) 25, 29 or 49 amino acids (aa) within each protomer RBD are not modeled, including 40% of the ACE-2 receptor binding site as measured by buried surface area (BSA) (Yan et al, 2020b).…”

Section: High Resolution Structure Of the Sars-cov-2 Rbdmentioning

confidence: 96%

“…Recently, the molecular structure of recombinant full-length SARS-CoV-2 Spike protein was solved in a stabilized pre-fusion state, by single particle cryo-Electron Microscopy (cryo-EM), at a resolution of 3.8 Å (Wrapp et al, 2020). Despite the comprehensive structural characterization of the spike protein as a whole, movement of the RBD between "up" and "down" conformational states prevented complete modeling of the RBD domains.…”

Section: Introductionmentioning

confidence: 99%

A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein

Joyce

Sankhala

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease-COVID-19within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus's surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 Å. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the "closed" prefusion S structure, but is accessible in "open" conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses. : bioRxiv preprint HIGHLIGHTSHigh resolution structure of the SARS-CoV-2 Receptor-Binding-Domain (RBD). Recognition of the SARS-CoV-2 RBD by SARS-CoV antibodies.Structure of the SARS-COV-2 RBD in complex with antibody CR3022.Identification of a cryptic site of vulnerability on the SARS-CoV-2 Spike.

show abstract

“…WHO formally designated the name of the novel coronavirus as COVID-19 on February 11th, 2020. The virus responsible for COVID-19 are deem as highly contagious infectious comparing with SARS, which caused cluster pneumonia cases emergence during the year 2002 and 2003 [2]. According to the Situation Report -28 released by the WHO, there are 71429 confirmed globally, among which there are 70635 confirmed in China [3].…”

Section: Introductionmentioning

confidence: 99%

Forecasting and Analysis of Time Variation of Parameters of COVID-19 Infection in China Using An Improved SEIR Model

Zhang

Pang

Xue

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Due to the emergency pandemic threat, the COVID-19 has attracted widespread attention around the world. Common symptoms of infection were fever, cough, and myalgia fatigue. On January 31, 2020, the World Health Organization (WHO) declares this outbreak a Public Health Emergency of International Concern (PHEIC).Methods: In order to study the spread of the novel coronavirus pneumonia, this paper proposed an improved SEIR model to simulate the spread of the virus, which includes the effect factor of government intervention. The model parameters are determined based on the daily reported statistical data (up to February 8) of confirmed, suspected, cured, and death. According to utilize the spread rate, the probability of infection of the suspected, the probability of the suspected becoming a confirmed one, the cure rate, the mortality rate, and the quarantine ratio, we performed simulations and parameter calibrations at three region levels, i.e., China, Hubei and non-Hubei respectively. In addition, considering that the government initiated effective prevention and control measures after the outbreak, this paper dynamically estimates all the parameters of the proposed model. Results:The simulation reveals that the parameters of non-Hubei region are not significantly different from Hubei's. Hubei Province has a high transmission rate, low cure rate, high probability of infection, low effective quarantine rate. since January 31, with the continuous strengthening of epidemic prevention and control measures, all parameters of the model have changed significantly. The parameters of Hubei and non-Hubei regions have the same trend. The trend of all parameters is now moving in a direction that is conducive to reducing the number of confirmed, suspected and fatal cases.Conclusions: The number of infections of the virus initially showed a rapid increase in the trend, and the number of infectious case showed a clear downward shape. With the government to take a variety of prevention and control measures and the efforts of the general medical staff, the number of infection curve on February 22 appeared in the top of the arc pattern, indicating that the inflection point began to appear, but the decline in the number of infections slowly.

show abstract

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

Cited by 1,351 publications

References 38 publications

On the origin and continuing evolution of SARS-CoV-2

On the origin and continuing evolution of SARS-CoV-2

A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein

Forecasting and Analysis of Time Variation of Parameters of COVID-19 Infection in China Using An Improved SEIR Model

Contact Info

Product

Resources

About