Sars cov 2 protein mutants

Scientists around the world are working to combat the new coronavirus. In addition to potential vaccines and therapies, they are also developing diagnostic tests, understanding the basic biology of the virus, and modeling the epidemiology.

Howard Hughes Medical Institute (HHMI) investigator Jesse Bloom and his colleagues have cataloged how nearly 4,000 different mutations alter the ability of SARS-CoV-2 to bind to human cells. Their data, publicly available online as an interactive map, is a new resource for researchers developing antiviral drugs and vaccines to combat COVID-19.

The HHMI study focused on mutations in the spike protein, a key part of SARS-CoV-2. This protein binds to a protein in human cells called ACE2, a necessary step for infection. Mutations in the spike protein could change the way SARS-CoV-2 attaches to and infects human cells. Bloom’s team generated yeast cells to display a fragment of the spike protein on their surface. This fragment, called the receptor-binding domain, comes into direct contact with ACE2.

The researchers created thousands of versions of the fragment, each with different mutations. They then measured how well these mutated fragments adhere to ACE2. The study data shows that many possible mutations could cause the virus to bind to human cells more strongly, but such mutations do not appear to be gaining ground in circulating versions of the virus.

The researchers found that other mutations made it difficult for the spike protein to attach to cells or prevent the protein from folding properly into its final form. Versions of the virus with these mutations are less likely to take hold because they cannot infect cells as effectively.

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