SARS-CoV-2 Spike full length (trimer form), D614

General information on SARS-CoV-2 Spike full length (variant 1), D614

SARS-CoV-2 is an enveloped positive-sense single-stranded RNA virus from the Coronavirus family. First identified in the Wuhan province (China) in December 2019 as the etiological agent of the COVID-19 disease, SARS-CoV-2 was soon classified as a pandemic strain that probably originated from animal reservoirs (zoonotic origin). The genome of the strain was shortly obtained allowing the design of fast response platforms for diagnostics and biotherapeutic/vaccine development. Like SARS-CoV-1, the new strain was found to adhere to human epithelial cells via its transmembrane structural protein known as the spike protein. The spike, one of the most abundant structural proteins on the envelope of this virus, is a complex and trimeric structure containing an N-terminal domain (S1 subunit) responsible for binding the human receptor ACE2 and a C-terminal domain (S2 subunit) responsible for forming the fusion core that mediates membrane fusion and viral internalization. The two units are linked by a furin cleavage site easily cleaved by ubiquitous proteases. This property has made the production of stable full-length forms of the spike protein rather challenging.

Several strategies can be used to overcome this limitation, at ProteoGenix, the full-length recombinant spike protein of SARS-CoV-2 was stabilized before its expression with targeted mutations to the furin cleavage site, considerably increasing its shelf-life without altering its original function. The stabilized variant can thus be used for studies that aim to further unravel the mechanism of infection in this new strain, but also serve in the development of diagnostic tools, targeted treatments, and vaccines.

The D614 variant of the spike was the dominant form of the protein during the early months of the epidemic when a sudden mutation in early March resulted in this position started gaining relevance (D614G, corresponding to a G-to-A base change at position 23,403 in the Wuhan reference strain). Data shows that the G614 variant, also known as the “G” clade, was first detected in Europe and then spread across the globe to become the dominant variant over a single month. In this context, the original D614 remains useful for comparative studies and further elucidation of SARS-CoV-2 mechanisms of infections.

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