The outbreak of a novel coronavirus (SARS-CoV-2) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV Spike Glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. The structure of SARS-CoV-2 Spike Glycoprotein 6VXX should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
SCIENCE recently published the work of Daniel Wrapp crystalizing the current generation of the SARS-CoV-2 Spike Glycoprotein, 2019-nCoV-2. Following the illustrations and supplemental materials describing each domain by amino acid sequence, a series of 3D models were generated for interactive exploration and 3D printing. In this publication, biomedical visualization scientists from Biologic Models translate these experimental results from the SCIENCE publication into 3-dimensional models which can be used to conduct a comprehensive comparative analysis of SAR-CoV-2 Spike Glycoprotein structure and function.
SARS-CoV-2 Spike Glycoprotein
The membrane-bound configuration of SARS-CoV-2 Spike Glycoprotein (PDB ID: 6VXX seen below) is a trimer At the top of each trimer complex is a receptor-binding domain (RBD green) that binds angiotensin-converting enzyme 2 (ACE2) with a higher affinity than does severe acute respiratory syndrome SARS-CoV S (2002). This in part is due to the unique modifications in the RBD that replace binding motifs with residues from a Pangolin virus (Dark green). Additionally, several published SARS-CoV S RBD-specific monoclonal antibodies were tested and found that they do not have appreciable binding to SARS-CoV-2, suggesting that antibody cross-reactivity may be limited because of the change to these residues (Dark Green). The structure of SARS-CoV-2 should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
Comparative Analysis of SARS-Cov-1 and 2019 SARS-Cov-2 NTD and RBD and the impact of Pangolin binding motif on ACE2 affinity can be explored in detail. HERE
SCIENCE Image Gallery
Text and Illustrations from SCIENCE publication: “Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.”
“The novel coronavirus 2019-nCoV has recently emerged as a human pathogen in the city of Wuhan in China’s Hubei province, causing fever, severe respiratory illness, and pneumonia—a disease recently named COVID-19 (1, 2). The emerging pathogen was rapidly characterized as a new member of the betacoronavirus genus, closely related to several bat coronaviruses and to severe acute respiratory syndrome coronavirus (SARS-CoV) (3, 4). Compared with SARS-CoV, 2019-nCoV appears to be more readily transmitted from human to human, spreading to multiple continents and leading to the WHO’s declaration of a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 (1, 5, 6).”
Biologic Model of SARS-CoV-2 Glycoprotein Spike 6vxx 3D printed in Full-color Sandstone or Multi-colored Plastic and colored to match “Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation” published recently in SCIENCE.