Exploring the Human-Coronavirus protein-protein interaction network from the perspective of a novel host-virus association

Abstract

Host-pathogen interaction is the best example of an evolutionary arms race where pathogen and host continuously coevolve to survive and exert negative effects on each other. The adaptability of both host and pathogen is critical for this association. In this study, we explored the association of severe acute respiratory syndrome (SARS) coronaviruses (CoVs) with their human host from the genomic and evolutionary perspectives based on a comparative analysis of SARS and MERS coronaviruses. We observed that human proteins that are part of the SARS-CoV2-human association are enriched in hubs and bottlenecks. Again, these proteins take part in more protein complexes and show slower evolutionary rates compared to the human proteins associated with the two other coronaviruses, SARS-CoV and MERS-CoV. Moreover, the human proteins involved in the interaction with SARS-CoV2 are mostly longer proteins harboring long intrinsically disordered stretches and a higher level of disordered protein binding sites. Codon usage analysis revealed that the novel coronavirus is least adapted to codons used in housekeeping and lung-specific genes, compared to the other two coronaviruses. We conclude that the signatures showed by the SARS-CoV2-human protein interaction network revealed the viruss association with vital human proteins and pathways, via interactions mediated by protein complexes and intrinsically disordered protein binding sites, which may have assisted the higher infectivity of SARS-CoV2 in its human host than the other two less-virulent human coronaviruses, despite having a lower optimization to its hosts codons.