Less is More. How removal of a few amino acids in the SARS-CoV-2 spike protein outsmarts the immune system

People systematically overlook subtractive changes. People tend to solve design challenges by adding extra elements even when taking something away would be simpler and more advantageous, according to an article in Nature today [1]. 

It took decades to think of removing pedals,
rather than adding stabilizers [2].

Common wisdom tells us that deletions in human texts cause loss of information. Almost by definition. The message is damaged. But is this wisdom also valid in genetic texts?

 

Enter the SARS virus. 

 

Can a deltion  in  genetic material have a positive effect? 

Can a deletion in genetic material have a positive effect? 

Variants of SARS-CoV-2 show the answer is: YES.

In January I blogged about the highly transmissible British variant [3]. This variant suffered from no less than 3 deletions [4]. Two occurred in the Spike protein. The British variant did not seem to be handicapped very much. On the contrary. At the time I didn't pay attention to the remarkable fact that deletions contributed to a positive effect. It didn't struck me as odd.

three deletions highlighted from [3].

Now I see that those deletions have a beneficial effect for the virus. (Not for us!). Nucleotide deletions in a specific part of Spike protein of SARS-CoV-2 may alter antigenicity. That means they normally provoke an immune response in the body. In this case that immune response is weaker. Specifically, deletion of amino acids 69 and 70 in the British variant B.1.1.7 resulted in a substantial higher infectivity of the virus. So, these the deletion of these amino acid seem to improve SARS-CoV-2 fitness. Deletion of amino acid 144 in B.1.1.7 variant and amino acids 242-244 in B.1.351 variant have also been associated with reduced binding capacity of certain neutralizing antibodies, and thus have a beneficial effect for the virus [5].

How can this LEGO structure be stabilised? [2]

When confronted with this LEGO structure with a blue supporting block in the left corner (see picture), and asked to stabilize the structure, most people add three supporting blocks in the remaining corners, but some simply removed the blue block. A simple and perfect solution. See video [2].

Evolution, found the same solution by trial and error. By removing a few amino acids, the virus has been improved.

I found the examples from everyday life helpful and inspiring. If you liked them too, please forward this blog post to your friends!

Fingerless Gloves (source)

Fingerless gloves: surprising result when you delete parts of the age-old design of a glove! Fingerless gloves are useful where dexterity is required that gloves would restrict. Cigarette smokers and church organists sometimes use fingerless gloves.

Postscript

In defense of the adding stabilizers to the bike: it's easier to add temporary stabilizers because they can easily be removed. So, one can use the same bike when the child is older. In contrast to the balance bike (loopfiets) where the pedals and chain, etc has to be removed. But that is a redesigned bicycle. But indeed, it is a much simpler bike! [21 Oct 2024]

 

Notes

1. People systematically overlook subtractive changes, Nature 8 April 2021
2. Less is more: Why our brains struggle to subtract, youtube 7 April 2021
   
3. Finding the highly transmissible British SARS-CoV-2 B.1.1.7 variant in the USA, blog 7 Jan 2021
   
4. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape, Science 12 Mar 2021 
5. SARS-CoV-2 Variants vs. Vaccines, American Society for Microbiology, March 3, 2021.
6. "The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein " 18 Mar 2021