Analysis of APOBEC and ADAR Deaminase-Driven Riboswitch Haplotypes in COVID-19 RNA Strain Variants and the Implications for Vaccine Design

Abstract

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.  Several studies already highlight how Riboswitches alter the 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, 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