Computational Search of Hybrid Human/ SARS-CoV-2 dsRNA Reveals Unique Viral Sequences That Diverge from Other Coronavirus Strains


The role of the RNAi/Dicer/Ago system to degrade RNA viruses has been elusive in mammals,which prompted authors to think that interferon (IFN) synthesis is essential in this clade relegatingthe RNAi defense strategy against viral infection as accessory function. We explore the theoreticalpossibilities that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in theopposite direction although this hypothesis seems counter intuitive. SARS-CoV-2 genome wastherefore computational searched for exact intra pairing within the viral RNA and also hybrid exactpairing with human transcriptome over a minimum 20 bases length. Minimal segments of 20 baseslength of SARS-CoV-2 RNA were found based on the theoretical matching with existingcomplementary strands in the human host transcriptome. Few human genes potentially annealingwith SARS-CoV-2 RNA, among them mitochondrial deubiquitinase USP30, a subunit of ubiquitinprotein ligase complex FBXO21 along with two long coding RNAs were retrieved. The hypothesisthat viral originated RNAi might mediate degradation of messengers of the host transcriptome wascorroborated by clinical observation and phylogenetic comparative analysis indicating a strongspecificity of these hybrid pairing sequences for both SARS-CoV-2 and human genomes.