COVID-19 Vaccines: A Modest Proposal

COVID-19 has become a global pandemic. With the introduction of vaccines the initial virus may have a chance to be controlled. However, mutants or variants, are being generated naturally at a fast rate and some are getting released by and into the existing pool of infected patients and spreading as a secondary pandemic. The question posed is: What can be done to address this secondary spread of new variants?

 The classic approach is to do a wait and see approach, seeing new infections, ascertain the variant, and then modify or enhance the vaccine to address that new variant. We see this in annual flu immunizations. Often this works well but there are times when one fails to see a new variant or the new variant arises after a set number of newer variants have been selected for vaccine preparations.

 A second approach may be possible. We examine this approach herein. Namely, we know several facts:

 1. COVID spike protein comes from an MRNA single stranded segment which is about 3000 nucleotides long generating a protein of about 1000 nucleic acids in length. We are being simplistic at this point.

 2. COVID spike protein targets the ACE2 receptor, ACE2R, on cells thus enabling entry, replication and immune responses.

 3. There are multiple ACE2 receptors so that the spike may be more infectious in some humans than others.

 4. We generally know what the pool of ACE2 receptors look like as proteins.

 5. We now know several COVID variants that attach to ACE2 receptors. We know or can know the nature of the spike/ligand binding sites. We know or can know the profiles of COVID variants and ACE2R variants and their binding strengths.

 6. We now know the putative genetic variants that are of concern and arguably we can ascertain the genetic changes that led from the wild type originally identified to each variant.

 7. We have many powerful computational tools to examine proteins, asses structure from RNA elements, and consider mutational changes. The challenge here may be a bit simpler since we know the ab initio protein structures and thus we deal with a boundary value problem having COVID and its variants on one end and ACE2R and its variants on the other.

 Thus, we pose the following challenge:

 1.     Knowing boundary condition proteins for spike and ACE2R, and assuming stability in ACE2R variants, then what mutations of the spike will lead to bindings to these ACE2R?

 2.     Furthermore, understanding these mutations can we rank order them from strongest binding downward?

 If we can achieve the two issues noted above, then it would be reasonable to anticipate the next set of most likely mRNAs for spikes and in turn use these anticipated spikes pre-emptively in a new vaccine profile.

 If correct, we can then develop a significant tamping down of infections prior to any substantial spread.