New mutations to the coronavirus that causes COVID-19 are emerging, including one in the United Kingdom with higher infection rates that has sparked new travel bans. Erik Procko, a professor of biochemistry at the University of Illinois Urbana-Champaign, has been studying mutations in the spike protein, the part of the virus that binds to human cells. In an interview with News Bureau biomedical sciences editor Liz Ahlberg Touchstone, Procko discussed the new variation and whether mutations to the spike protein could create resistance to vaccines or other treatments.
What is the “spike” protein on the virus that causes COVID-19, and why are mutations to it concerning?
The surface of the virus is decorated with proteins that stick out and look like molecular spikes. The spike proteins bind to a receptor on our own cells, called ACE2, which triggers virus entry and infection. Furthermore, our antibody defenses primarily recognize these spikes to provide immunity. This means that any mutations in the virus spike can impact how well the virus infects cells and how well antibodies block the virus to provide immunity.
What is the new variant of the virus circulating in the United Kingdom? How different is it from the version circulating in the United States?
The new virus variant in the U.K., known as the B.1.1.7 lineage, has accumulated 14 lineage-specific mutations. The exact roles of these mutations remain unclear, but there is evidence that this variant is more transmissible. In particular, two mutations in the spike are of concern. One mutation affects processing of the spike protein and the second, called N501Y, resides exactly where the spike binds the cell receptor.
You have been looking at various mutations to the spike protein. What can you tell us about the mutations in the new variant?
We have been developing decoy receptors as therapeutics to potently block infection of SARS-CoV-2, the coronavirus that causes COVID-19. As part of this work, we screened mutations in the spike that may reduce the effectiveness of the decoys and provide the virus with resistance. We found several mutations that make the virus spike bind more tightly to the human receptor. The N501Y mutation – the one we see in the U.K. variant – stood out to us, as it had 20 times greater affinity for the receptor. This finding may explain in part why the B.1.1.7 lineage appears to be more infectious, although other mutations almost certainly are important too, and further research is needed. But it is concerning.
What are the “decoy receptors” you developed?
Decoy receptors are engineered versions of the natural ACE2 receptor that can block the spike from binding to the natural receptors on our cells. In this way, decoys work similarly to antibodies, but the virus has less opportunity to become resistant because mutations that reduce binding to the decoy simultaneously reduce binding to the natural human receptor, making the virus less infectious.
Could any of the mutations you’ve studied so far give the virus resistance to the vaccines being developed? Why or why not?
I doubt any single mutation will make the virus resistant to the vaccines under development. After immunization, our bodies produce many different antibodies that bind to different sites on the virus spike. For the virus to become fully resistant, it would need to accumulate multiple mutations at all these different sites. That could certainly happen, but it will take time. The scientific community must be vigilant in tracking new virus variants so manufacturers can adjust vaccines as necessary.
You found that your decoy receptors broadly bind to the varying spike proteins of different strains. What does this suggest for how treatments or vaccinations could work against varying mutations?
Our work shows SARS-CoV-2 is unlikely to become resistant to a decoy receptor through mutations in the spike. The decoy receptor also binds tightly to the spikes of other coronaviruses from bats that use the same human receptor. While drug development takes enormous resources and effort, it suggests decoy receptors could be developed to safeguard against new SARS-CoV-2 strains or even future crossovers of SARS-associated coronaviruses from animals.
