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I wish to investigate how a virus could be attenuated through targeted mutagenesis by investigating its protein mutations in order to produce an efficacious vaccine. Are there examples where the protein sequence of exisiting vaccine strains have been compared against their wild-type counterparts to understand the mechanism of virulence/attenuation? Secondly which viral proteins are the focus of such studies?

I am a computer scientist looking for a mathematical approach towards understanding the mutational parameter space of viral protein sequence data, for example through a mutational correlation matrix between vaccine and wild type protein sequence. This may have application for example to COVID-19.

I wish to investigate how a virus could be attenuated through targeted mutagenesis by a priori prediction of attenuating amino acid mutations.

In particular, I am seeking bioinformatic solutions where the protein sequence of an exisiting live vaccine strais has been compared against it wild-type counterparts to identify key attenuating mutations and the key attenuating mutation(s) can be deduced without wet-lab site directed mutagenesis.

I presume surface antigens, such as the spike protein in COVID-10 would be the proteins of interest, but I'm open to suggestions.

I am a computer scientist looking to investigate the mutational parameter space of viral protein sequence data. A key approach I am considering is to use a mutational correlation/covariance matrix and then remove convolution artefacts. I hope this will identify compensatory mutations that will maintain a local interaction for example within a fold, providing a starting point for identifying attenuating mutations. 

This may have application for example to COVID-19 and the goal is to produce an efficacious vaccine.