Selecting monkeypox virus drug targets and antiviral drugs based on protein-protein interaction networks

Objective Construct a protein interaction network between monkeypox virus (MPXV) and humans. Through the analysis of this network, identify monkeypox virus proteins and human proteins as potential drug targets, and predict antiviral drugs.Methods The interaction network between MPXV and human proteins (MIP) was established based on the P-HIPSTer database. MPXV proteins in the established interaction network were selected as drug targets by calculating the centrality, conservation, and immunogenicity of virus proteins. A protein interaction network was established between MIP and human proteins. Through the analysis of network topology properties, the most important MIP (abbreviated as MMIP) were identified as potential drug targets. An interaction network between MIP and other viruses was established, and within MMIP, broad-spectrum drug target proteins were further screened. Functional enrichment of MIP genes was conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, performed with the “clusterProfiler” package in R. Finally, drugs targeting MPXV and human proteins identified in the above steps were predicted based on the DrugBank database.Results The protein interaction network between MPXV and humans was constructed, which contained 4591 non-redundant protein-protein interactions between 70 virus proteins and 2,218 human proteins (abbreviated as MIP). Three MPXV proteins, OPG083, OPG084, and OPG190, were identified as drug targets. The 86 the most important MIPs (MMIPs) were selected as potential drug target. An interaction network between MIP and proteins from other viruses revealed 31 MMIPs as potential broad-spectrum drug targets. Functional analysis of MIP indicated enrichment in infection and immune system pathways. A total of 85 drugs were identified to act on MPXV proteins, and 371 drugs on human proteins. Among them, fostamatinib, trilostane and raloxifen are capable of simultaneously inhibiting both virus and host proteins in the interaction network between MPXV and humans.Conclusion A protein interaction network between MPXV and humans was established. OPG083, OPG084, and OPG190 were identified as drug targets, while 31 human proteins were recognized as potential targets against MPXV. A total of 453 drugs were predicted to inhibit virus infection by disrupting the virus-host interaction protein-protein interaction (PPI) network, with priority given to validating drugs such as fostamatinib, trilostane and raloxifen.