Impact Analysis of SARS-CoV2 on Signaling Pathways during COVID19 Pathogenesis using Codon Usage Assisted Host-Viral Protein Interactions

Abstract

Understanding the molecular mechanism of COVID19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The pathogen may target cell signaling pathways to disrupt the pathway genes’ regular activities, resulting in disease. Understanding the interaction mechanism of viral and host proteins involved in different signaling pathways may help decipher the attacking mechanism on the signal transmission during diseases, followed by discovering appropriate therapeutic solutions.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). Exploiting 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 codon usage pattern similarity (and dissimilarity), we propose a computational scheme to recreate the hostviral protein interaction network (HVPPI). We use seventeen (17) essential signaling pathways for our current work and study the possible targeting mechanism of SARS-CoV2 viral proteins on such pathway proteins. We infer both negatively and positively interacting edges in the network. We can find a relationship where one host protein may target by more than one viral protein.Extensive analysis performed to understand the 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. In ranking the most affected pathways, MAPK pathways observe to be worst affected during the COVID-19 disease. A good number of targeted proteins are highly central in host protein interaction networks. Proteins participating in multiple pathways are also highly connected in their own PPI and mostly targeted by multiple viral proteins.

Data science in unveiling COVID-19 pathogenesis and diagnosis: evolutionary origin to drug repurposing

“…SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, mouse MHV, avian IBV) obtaining a SARS-CoV-2 phylogenetically close interactome. As a novel attempt [ 109 ], the codon pattern is used to infer possible interactions between 26 SARS-CoV-2 proteins and selective host proteins involved in 17 major cell signalling pathways.…”