Host-mediated RNA editing in viruses.

Viruses rely on hosts for life and reproduction, cause a variety of symptoms from common cold to AIDS to COVID-19 and provoke public health threats claiming millions of lives around the globe. RNA editing, as a crucial co-/post-transcriptional modification inducing nucleotide alterations on both endogenous and exogenous RNA sequences, exerts significant influences on virus replication, protein synthesis, infectivity and toxicity. Hitherto, a number of host-mediated RNA editing sites have been identified in diverse viruses, yet lacking a full picture of RNA editing-associated mechanisms and effects in different classes of viruses. Here we synthesize the current knowledge of host-mediated RNA editing in a variety of viruses by considering two enzyme families, viz., ADARs and APOBECs, thereby presenting a landscape of diverse editing mechanisms and effects between viruses and hosts. In the ongoing pandemic, our study promises to provide potentially valuable insights for better understanding host-mediated RNA editing on ever-reported and newly-emerging viruses.

Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades.

COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a staggering pandemic in a few months, and a global fight against both has been intensifying. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code to molecular mechanisms, based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on the replicase-transcriptase complex. Our analysis starts with primary sequence information, identity-based phylogeny based on 22,051 SARS-CoV-2 sequences, and evaluation of sequence variation patterns as mutation spectra and its 12 permutations among organized clades. All are tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings are listed as follows: 1) The most dominant mutation is C-to-U permutation, whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity, albeit assumed most slightly deleterious. 2) The second abundance group includes three negative-strand mutations (U-to-C, A-to-G, and G-to-A) and a positive-strand mutation (G-to-U) due to DNA repair mechanisms after cellular abasic events. 3) A clade-associated biased mutation trend is found attributable to elevated level of negative-sense strand synthesis. 4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral proteome changes. These findings demand a platform where emerging mutations are mapped onto mostly subtle but fast-adjusting viral proteomes and transcriptomes, to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applications. Such actions are in desperate need, especially in the middle of the War against COVID-19.