Researchers Have Created The First 3D Map Of A Key Coronavirus Protein

This is a 3D atomic scale map, or molecular structure, of the 2019-nCoV spike protein. The protein takes on two different shapes, called conformations -- one before it infects a host cell and another during infection. This structure represents the protein before it infects a cell, called the prefusion conformation. Credit: Jason McLellan/Univ. of Texas at Austin

A team of scientists from the University of Texas at Austin and the National Institutes of Health have produced the first 3D atomic-scale map of a key protein used by 2019-nCoV, the new coronavirus that infects humans. The discovery could be vital in the production of an effective vaccine against the disease.

The team mapped a part of the virus called a spike protein that attaches itself to human cells and infects them. The study, published in Science, details the protein structure, indicating its similarities and differences with the SARS coronavirus. The work also reveals that the antibodies for SARS are not effective against the new virus.

The team obtained the structure so quickly thanks to their experience studying other coronaviruses such as SARS-CoV and MERS-CoV. This allowed them to use methods already in place to lock the spike proteins to better analyze them.

“As soon as we knew this was a coronavirus, we felt we had to jump at it,” senior author Jason McLellan, an associate professor at UT Austin, said in a statement. “because we could be one of the first ones to get this structure. We knew exactly what mutations to put into this, because we’ve already shown these mutations work for a bunch of other coronaviruses.”

The discovery was possible thanks to the cryogenic electron microscopy (cryo-EM) technique. With this, samples are cooled down to -150℃ and then bombarded with a stream of electrons. By registering how these electrons bounce around, the team can reconstruct the 3D shape of the molecules.

The work confirms independent analyses that suggest the entry point of the 2019-nCoV into human cells is the ACE2 receptor. This was also the case for SARS, but the new virus has 10 times the affinity for this receptor than the SARS coronavirus. It's possible this affinity could be contributing to the new coronavirus' ability to transmit between humans so easily, although the authors warn that more studies are needed to be certain.

The spike protein has two conformations (or two shapes) – one before it infects the host cells and one during the infection. The team created a map of the pre-infection shape of the protein (pictured above), also known as the prefusion conformation. 
 
Since the team managed to reconstruct molecules on the spike protein's surface, the part that produces an immune response, they now plan to use this to isolate the right antibodies in patients that have recovered from the infection. This could be used to treat a 2019-nCoV infection after exposure. While the work is encouraging, a successful vaccine is likely still many months, if not longer, away.
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