Some Of SARS-CoV-2 Mutations Are In Response To Human Proteins

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Mutations are a standard phenomenon in the genetics of organisms — some lead to advantages, some negatively affect organisms, and some don’t have any effects. It should come as no surprise then that researchers have been looking at how SARS-CoV-2, the virus responsible for Covid-19, is mutating.

In an analysis of over 15,000 SARS-CoV-2 genomes, the team uncovered more than 6,000 mutations. However, some of the mutations did not appear to be random. The team believes that some of the mutations in the virus genome were caused by a human protein called APOBEC. This is not that surprising as APOBEC is known for affecting the genetic code of viruses that infect human cells. The findings are reported in the journal Molecular Biology and Evolution.

“I have looked at mutational profiles for many organisms and they all show some sort of bias, but I’ve never seen one as strong and strange as this,” senior author Professor Laurence Hurst, director of the Milner Centre for Evolution at the University of Bath, said in a statement.

The genetic code of most viruses are based on RNA alone and not DNA like us. RNA is made using a series of nitrogenous bases of guanine, adenine, and cytosine, (G, A, C), which are also used by DNA, and a fourth one known as uracil (DNA uses thymine). Mutations happen when these bases are swapped out of place, possibly altering how the particular organism works.

The researchers found there is a strong mutation bias against uracil (U), in particular in regions where two of these molecules are next to each other (UU).  In fact, the UU content in the genes analyzed were about one-quarter of what they had predicted. 

It's possible APOBEC is increasing the U content in the virus' genetic code and this produces variants that don't survive, a possible negative mutation. This is why they are not appearing in the sample. Those that appear are the viruses that have not been affected much by the protein. Essentially, some versions of the virus are surviving better in our cells than others, and this knowledge could be exploited for therapies and making a vaccine.

Current research has focused on creating an immune response from viruses engineered to have the same proteins on their outer shell as SARS-CoV-2. If these findings are confirmed, it may be possible to alter SARS-CoV-2 directly to create an attenuated version of the virus, one that cannot harm us but it can train our immune cells.

“Knowing what selection favours and disfavours in the virus is really helpful in understanding what an attenuated version should look like,” Professor Hurst added. “We suggest for example that increasing U content, as APOBEC does within our cells, would be a sensible strategy.”

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