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Comparative host-pathogen protein-protein interaction analysis of recent coronavirus outbreaks and important host targets identification.

ABSTRACT: Last two decades have witnessed several global infectious outbreaks. Among these, coronavirus is identified as a prime culprit ranging from its involvement in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) to COVID-19. These infections involved in huge healthcare and economic cost incurred globally. Every time, coronavirus improved its infection ability and surprised the medical practitioners and researchers. Currently, COVID-19 is also causing numerous infections and stalled global activities. Global efforts are underway to identify potential viral targets for management of these outbreaks, but significant progress in prevention of these outbreaks is not yet achieved. We explored host-pathogen protein-protein interactions of MERS, SARS and COVID-19, and identified host targets common among all recent coronavirus outbreaks. Further, we tried to understand their potential for management of coronavirus. The common proteins involved in coronavirus host-pathogen interactions indicate their indispensable role in the pathogenesis and therefore targeting these proteins can give strategies to prevent current and future coronavirus outbreaks. Viral variability necessitates development of new therapeutic modalities for every outbreak, in contrast targeting necessary human proteins required by all coronaviruses can provide us a clue to prevent current and future coronavirus outbreaks. We found that targeting FURIN and TMPRSS2 can provide good results due to their common involvement in current and previous outbreaks. We also listed some known molecules against these two targets for their potential drug repurposing evaluation. Although, several recent studies undergoing with targeting these proteins for management of coronavirus, but safety evaluation and risk assessment must be given prime importance while targeting human proteins.

SUBMITTER: Khan AA

PROVIDER: S-EPMC7546044 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Comparative host-pathogen protein-protein interaction analysis of recent coronavirus outbreaks and important host targets identification.

Khan Abdul Arif AA Khan Zakir Z

Briefings in bioinformatics 20210301 2

Last two decades have witnessed several global infectious outbreaks. Among these, coronavirus is identified as a prime culprit ranging from its involvement in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) to COVID-19. These infections involved in huge healthcare and economic cost incurred globally. Every time, coronavirus improved its infection ability and surprised the medical practitioners and researchers. Currently, COVID-19 is also causing numerous infecti ...[more]

PMID: 32914167

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Project description:BackgroundInfectious diseases are a cruel assassin with millions of victims around the world each year. Understanding infectious mechanism of viruses is indispensable for their inhibition. One of the best ways of unveiling this mechanism is to investigate the host-pathogen protein-protein interaction network. In this paper we try to disclose many properties of this network. We focus on human as host and integrate experimentally 32,859 interaction between human proteins and virus proteins from several databases. We investigate different properties of human proteins targeted by virus proteins and find that most of them have a considerable high centrality scores in human intra protein-protein interaction network. Investigating human proteins network properties which are targeted by different virus proteins can help us to design multipurpose drugs.ResultsAs host-pathogen protein-protein interaction network is a bipartite network and centrality measures for this type of networks are scarce, we proposed seven new centrality measures for analyzing bipartite networks. Applying them to different virus strains reveals unrandomness of attack strategies of virus proteins which could help us in drug design hence elevating the quality of life. They could also be used in detecting host essential proteins. Essential proteins are those whose functions are critical for survival of its host. One of the proposed centralities named diversity of predators, outperforms the other existing centralities in terms of detecting essential proteins and could be used as an optimal essential proteins' marker.ConclusionsDifferent centralities were applied to analyze human protein-protein interaction network and to detect characteristics of human proteins targeted by virus proteins. Moreover, seven new centralities were proposed to analyze host-pathogen protein-protein interaction network and to detect pathogens' favorite host protein victims. Comparing different centralities in detecting essential proteins reveals that diversity of predator (one of the proposed centralities) is the best essential protein marker.

Dataset Information

Comparative host-pathogen protein-protein interaction analysis of recent coronavirus outbreaks and important host targets identification.

Publications

Comparative host-pathogen protein-protein interaction analysis of recent coronavirus outbreaks and important host targets identification.

Similar Datasets

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