Photo Credit: Marina Demidiuk

The following is a summary of “Expression analysis and mapping of Viral—Host Protein interactions of Poxviridae suggests a lead candidate molecule targeting Mpox,” published in the May 2024 issue of Infectious Disease by Loganathan et al.

Researchers conducted a retrospective study investigating the interaction between Monkeypox virus (MPXV) and host cells, aiming to illuminate potential therapeutic targets for this important human pathogen.

They analyzed GEO Expression datasets to characterize mRNA profile changes in various host responses to poxviruses. Protein-protein interaction (PPI) maps were built. The viral gene expression datasets of MPXV and Vaccinia virus (VACV) were utilized to pinpoint significant viral genes and explore the binding to a library of targeting molecules.

The results showed that infection with MPXV affects various cellular pathways, including interleukin and MAPK signaling. While most host differentially expressed genes (DEGs) are primarily downregulated upon infection, there are notable enrichments in histone modifiers and immune-related genes. The PPI analysis showed a novel virus-specific PPI for the genes in the aforementioned functional clusters. The viral DEGs displayed varying expression patterns across three studied cell types: primary human monocytes, primary human fibroblast, and HeLa, resulting in 118 commonly deregulated proteins. Poxvirus proteins C6R-derived protein K7 and K7R of MPXV and VACV were prioritized as targets for potential therapeutic interventions due to their histone-regulating and immunosuppressive properties. In computational docking and Molecular Dynamics (MD) experiments, the proteins were demonstrated to bind the candidate small molecule S3I-201, further prioritized for lead development.

Investigators concluded that MPXV weakens the cell’s antiviral defenses through histone modification and immune evasion, highlighting S3I-201, a molecule binding to the C6R-derived protein K7, as a promising candidate drug for Mpox treatment.

Source: bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09332-x