Fighting SARS-CoV-2 and other viruses with RNA bioinformatics

Abstract

RNA viruses cause millions of infections in humans and animals every year, thereby challenging health systems and economies globally. Large-scale outbreaks of emerging and re-emerging agents, such as Dengue, Zika, Chikungunya, and Ebola virus in human and African swine fever virus in animals have been reported over the last years. These outbreaks can reveal new clinical manifestations, e.g., the accumulation of congenital microcephaly cases during the Zika virus epidemic in the Americas 2015-2016. Very recently, the emergence of a novel pneumonia (COVID-19) in the city of Wuhan, China, and its subsequent worldwide spread, has been associated with a novel coronavirus, SARS- CoV-2. Thanks to the rapid availability of dozens of full-length SARS-CoV-2 genomic sequences, phylogenetic proximity to known pathogens like SARS and MERS could be established. On a more fine-grained scale, SARS-CoV-2 shares ancestral roots with coronaviruses isolated from bats and pangolins.
While vaccines are only available for a few viruses, and the biochemical mechanisms that mediate tropism and pathology are often poorly understood, experimental data suggest an involvement of RNA structure in many of these viral pathologies. Comparative studies of RNA structure combine thermodynamic and kinetic modeling, phylogenomics, and homology search, thereby providing a powerful approach for characterizing the evolutionary conservation of viral genomes. Here, the availability of large amounts of genome data allows building fine-grained models of homologous RNA structures in phylogenetically related viruses. Typically, the untranslated regions (UTRs) of virus genomes harbor functional RNA elements, which play vital roles in viral translation, replication, pathogenesis, and host adaptation. Novel data from comparative RNA bioinformatics screens also provide evidence for the existence of many evolutionarily conserved RNA structures within the coding regions of SARS-CoV-2 and related coronaviruses. While many of these structures have not been previously described, they reveal characteristic patterns of evolutionarily conserved RNAs inside and outside of coronavirus coding regions. In this line, they represent potential targets for vaccine development and novel antiviral drugs.