In a boost to vaccine development, structure of SARS-CoV-2 spike protein mapped

3d - map
The atomic-level structure of the SARS-CoV-2 spike protein in its prefusion conformation. The receptor binding domain, the part of the spike that binds to the host cell, is coloured green. Photo credit: UT Austin, McLellan Lab

U.S. researchers have 3D mapped the spike protein of the novel coronavirus. Unlike SARS, the spike protein of SARS-CoV-2 shows 10- to 20-fold higher affinity to bind to the human receptor ACE2. The higher binding affinity could be the reason for greater human spread.

Researchers at the University of Texas at Austin and the National Institutes of Health have produced a 3D atomic scale map of the protein of the novel coronavirus (SARS-CoV-2) that binds to and infects human cells.

Mapping the 3D structure of the protein — spike (S) glycoprotein — will allow better understanding of how the virus binds to the human cells. Knowing the structure of the spike protein will, in turn, allow scientists to develop vaccines and antivirals against the virus and even better diagnostics.

Like other coronaviruses, SARS-CoV-2 virus particles are spherical and have mushroom-shaped proteins called spikes protruding from their surface, giving the particles a crown-like appearance. The spike binds and fuses to human cells, allowing the virus to gain entry.

The spike protein of the novel coronovirus shares 98% sequence identity with the spike protein of the bat coronavirus, the researchers say. The results were published in the journal Science.

The researchers also found that like in the case of SARS coronavirus, the spike protein of the novel coronavirus (SARS-CoV-2) that causes COVID-19 disease also binds to the cellular receptor called angiotensin-converting enzyme 2 (ACE2), which serves as the entry point into human cells.

Greater binding affinity

But unlike in the case of the SARS, the spike protein of the novel coronavirus binds to the cell receptor with much higher affinity — 10- to 20-fold higher. The much greater binding affinity to the cell receptor explains the apparent high human-to-human transmissibility of the virus compared with the SARS coronavirus.

“The high affinity of the 2019-nCoV S for human ACE2 may contribute to the apparent ease with which the 2019-nCoV can spread from human-to-human,” they write. “Additional studies are needed to investigate this possibility.”

Existing antibodies not useful

Since both the SARS coronavirus and the 2019 novel coronavirus share structural similarity and bind to the same receptor, the researchers tested three monoclonal antibodies specific to SARS virus for their ability to bind to the novel coronavirus. But none of the three antibodies tested were found to be effective in inhibiting the novel coronavirus from binding to the human receptor ACE2 and prevent or treat the disease.

However, the 3D map of the S protein will help researchers design new antivirals to stop the virus from binding and infecting human cells.

“Knowing the atomic-level structure of the 2019-nCoV spike will allow for additional protein engineering efforts that could improve antigenicity and protein expression for vaccine development,” the researchers write.

The researchers were able to determine the structure of the spike protein as the Chinese researchers shared the whole genome sequence data in the global database.

Published in The Hindu on February 22, 2020