Analysis of APOBEC and ADAR deaminase driven Riboswitch Haplotypes in COVID 19 RNA strain variants and the implications for mono strain vaccine design
This paper reports the results of our initial analysis of APOBEC and ADAR deaminase mediated mutation signature patterns in complete COVID 19 genomes from informative locations and times in China, USA and Spain in the 2019 2020 pandemic. We have identified a unique set of 'new' putative coordinated Riboswitches in COVID 19 genomes not previously identified, and likely generating variants of the known common strain Haplotypes now in circulation. The results reveal that COVID 19 diversifies using switching of RNA Haplotypes with minimal alteration to protein structure (the normal targets for B and T cells in conventional vaccine development) The deaminase driven RNA Haplotypes are most likely aligned with RNA secondary structures as several studies already highlight how Riboswitches alter he ability of RNA to fold into intricate three dimensional structures allowing them to execute their diverse cellular functions. The same functional outcomes are expected for viruses, particularly efficacy of RNA replication in new host cell environments. Thus, monostrain vaccine designs that assume that the main viral protein antigens will be the only putative protective targets could fail to produce effective and protective immunity. We conclude that understanding COVID 19 adaptation and survival strategy and identifying the host Haplotype, and which vaccine(s) is effective for each Haplotype group will be important for new vaccine design. Our study also has wider implications for the actual origins and spread of COVID 19 but these will be pursued in future publications.