Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus which caused the coronavirus disease 2019 pandemic and infected more than 12 million victims and resulted in over 560,000 deaths in 213 countries around the world. Having no symptoms in the first week of infection increases the rate of spreading the virus. The increasing rate of the number of infected individuals and its high mortality necessitates an immediate development of proper diagnostic methods and effective treatments. SARS-CoV-2, similar to other viruses, needs to interact with the host proteins to reach the host cells and replicate its genome. Consequently, virus-host protein-protein interaction (PPI) identification could be useful in predicting the behavior of the virus and the design of antiviral drugs. Identification of virus-host PPIs using experimental approaches are very time consuming and expensive. Computational approaches could be acceptable alternatives for many preliminary investigations. In this study, we developed a new method to predict SARS-CoV-2-human PPIs. Our model is a three-layer network in which the first layer contains the most similar Alphainfluenzavirus proteins to SARS-CoV-2 proteins. The second layer contains protein-protein interactions between Alphainfluenzavirus proteins and human proteins. The last layer reveals protein-protein interactions between SARS-CoV-2 proteins and human proteins by using the clustering coefficient network property on the first two layers. To further analyze the results of our prediction network, we investigated human proteins targeted by SARS-CoV-2 proteins and reported the most central human proteins in human PPI network. Moreover, differentially expressed genes of previous researches were investigated and PPIs of SARS-CoV-2-human network, the human proteins of which were related to upregulated genes, were reported.

<abstract> <p>More than ten million deaths make influenza virus one of the deadliest of history. About half a million sever illnesses are annually reported consequent of influenza. Influenza is a parasite which needs the host cellular machinery to replicate its genome. To reach the host, viral proteins need to interact with the host proteins. Therefore, identification of host-virus protein interaction network (HVIN) is one of the crucial steps in treating viral diseases. Being expensive, time-consuming and laborious of HVIN experimental identification, force the researches to use computational methods instead of experimental ones to obtain a better understanding of HVIN. In this study, several features are extracted from physicochemical properties of amino acids, combined with different centralities of human protein-protein interaction network (HPPIN) to predict protein-protein interactions between human proteins and Alphainfluenzavirus proteins (HI-PPIs). Ensemble learning methods were used to predict such PPIs. Our model reached 0.93 accuracy, 0.91 sensitivity and 0.95 specificity. Moreover, a database including 694522 new PPIs was constructed by prediction results of the model. Further analysis showed that HPPIN centralities, gene ontology semantic similarity and conjoint triad of virus proteins are the most important features to predict HI-PPIs.</p> </abstract>

Background Infectious 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. Results As 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. Conclusions Different 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.

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