Researchers Create 3D Map of Protein Used by SARS-CoV-2 to Invade Cells

Researchers Create 3D Map of Protein Used by SARS-CoV-2 to Invade Cells

The 2019 Novel Coronavirus, SARS-CoV-2, which causes the disease COVID-19 in humans, has spread around the world rapidly, far faster and to a much greater extent than similar coronaviruses such as those that caused SARS (SARS-CoV) and MERS.

In order to understand the difference between SARS-CoV-2, SAR-CoV, and other coronaviruses, and the impact on infectivity, pathogenesis, and the host range, scientists need to identify the receptor recognition mechanism of the virus.

Researchers at the University of Minnesota have been studying SARS-CoV-2 using X-ray crystallography and have created a 3D map of the spikes on the surface of the virus that are used to bind to human cells.

Both SARS-CoV and SARS-CoV-2 bind to the same receptor on human cells: human ACE2 (hACE2) However, SARS-CoV-2, binds much more strongly to the receptor than SARS-CoV. The research suggest that the stronger binding mechanism means when the virus is inhaled through the nose or mouth, there is a much higher chance of the virus binding to a hACE2 receptor than was the case with SAR-CoV.

“The 3D structure shows that compared to the virus that caused the 2002-2003 SARS outbreak, the new coronavirus has evolved new strategies to bind to its human receptor, resulting in tighter binding,” explained lead researcher, Dr Fang Li. “The tight binding to the human receptor can help the virus infect human cells and spread among humans.”

The ability of the virus to bind more tightly with the hACE2 receptor allows cells to be infected in the upper respiratory tract (nose, mouth and throat) in contrast to SARS-CoV, where infection most commonly occurred in the lungs.

There are fewer hACE2 receptors on cells in the upper respiratory tract so more efficient binding is required to infect those cells. This provides clues to the reason why the virus has spread much faster and more widely. If cells in the upper respiratory tract are infected, transmission to others becomes much more likely.

The 3D map created by the researchers can be used to find molecules that can bind to the spikes on the virus more strongly and at higher frequency than the hACE2 receptor on cells, which would help to block the virus and prevent it from entering cells.

The researchers also made comparisons between SARS-CoV-2 and other coronaviruses that have been discovered in bats, with their research also supporting the theory that SARS-CoV-2 evolved in bats before making the jump to humans, either directly or through another species such as pangolins.

You can read more about the study in the paper –Structural basis of receptor recognition by SARS-CoV-2 – which was recently published in the journal Nature. DOI: 0.1038/s41586-020-2179-y

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