A Scheme for Inferring Viral-Host Associations based on Codon Usage Patterns Identifies the Most Affected Signaling Pathways during COVID-19

Das, Jayanta Kumar; Chakraborty, Subhadip; Roy, Swarup

Understanding the molecular mechanism of COVID-19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The expression of any viral gene depends mostly on the host translational machinery. Recent studies report the great significance of codon usage biases in establishing host-viral protein-protein interactions (PPI). Exploring the codon usage patterns between a pair of co-evolved host and viral proteins may present novel insight into the host-viral protein interactomes during disease pathogenesis. Leveraging the similarity (and dissimilarity) in codon usage patterns, we propose a computational scheme to recreate the host-viral protein-protein interaction network. We use host proteins from seventeen (17) essential signaling pathways for our current work towards understanding the possible targeting mechanism of SARS-CoV-2 viral proteins. We infer both negatively and positively interacting edges in the network. Further, extensive analysis is performed to understand the host PPI network topologically and the attacking behavior of the viral proteins. Our study reveals that viral proteins mostly utilize codons, rare in the targeted host proteins (negatively correlated interaction). Among non-structural proteins, NSP3 and structural protein, Spike (S) protein, are the most influential proteins in interacting multiple host proteins. While ranking the most affected pathways, MAPK pathways observe to be the worst affected during the COVID-19 disease. Several proteins participating in multiple pathways are highly central in host PPI and mostly targeted by multiple viral proteins. We observe many potential targets (host proteins) from the affected pathways associated with the various drugs molecules including Arsenic trioxide, Dexamethasone, Hydroxychloroquine, Ritonavir, and Interferon beta, which are either under trail or in use during COVID-19.