Studies on Human-Coronavirus protein-protein interaction network from the perspective of viral adaptation in a novel host

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 adaptation of the severe acute respiratory syndrome (SARS) coronavirus (CoV) in humans from the genomic and evolutionary perspectives based on a comparative analysis of SARS-CoV2-human and Other-CoV-human interactions. We observed that human proteins that are part of the SARS-CoV2-human association are less enriched in hubs and bottlenecks. Again, they also take part in fewer protein complexes and show faster evolutionary rates compared to the Other-CoV-associated human proteins. The human proteins involved in the interaction with SARS-CoV2 are mostly longer proteins harboring long disordered stretches and a higher level of disordered protein binding sites. Codon usage analysis also revealed that the novel coronavirus is least adapted to codons, used in housekeeping genes and genes that get expressed in lung tissues, compared to other two deadly coronaviruses, SARS CoV1 and MERS CoV. We conclude that the signatures showed by SARS-CoV2-human protein interaction network represent a model for understanding the evolutionary feature of an early stage of host-virus association in comparison to that obtained from relatively long-term-associated host-virus interactions, achieving higher levels of adaptation.ImportanceThe current study focuses on the evolution of viruses, using novel coronavirus as a model. The host-pathogen interaction is better viewed from molecular perspective, where host and pathogen proteins interact and co-evolve with each other. This is even more important for viruses, which use the host’s cellular machinery for protein synthesis. As for a deadly virus, killing the host is inadvertent as it is also suicidal for the virus itself. A more stable association that is beneficial for both host and virus will require host adaptation, achievable through evolutionary time. In this study, the deadly novel human coronavirus has been viewed as the early stage of host viral interaction, which has been achieved through a more random way, with lower adaptation to host codons compared to the other human coronaviruses, having more stable host-association for being evolutionarily older.