Expression analysis and mapping of Viral-Host Protein interactions of Poxviridae suggests a lead candidate molecule targeting Mpox.

Autor: Loganathan T; Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore-632014, Tamil Nadu, India., Fletcher J; Department of Clinical Virology, Christian Medical College, Tamil Nadu, Vellore, 632004, India., Abraham P; Department of Clinical Virology, Christian Medical College, Tamil Nadu, Vellore, 632004, India., Kannangai R; Department of Clinical Virology, Christian Medical College, Tamil Nadu, Vellore, 632004, India., Chakraborty C; School of Life Science and Biotechnology, Adamas University, Kolkata, India., El Allali A; Bioinformatics Laboratory, College of Computing, Mohammed VI Polytechnic University, Ben Guerir, Mohammed, Morocco. achraf.ELALLALI@um6p.ma., Alsamman AM; Department of Genome Mapping, Molecular Genetics, and Genome Mapping Laboratory, Agricultural Genetic Engineering Research Institute, Giza, Egypt., Zayed H; Department of Biomedical Sciences College of Health Sciences, QU. Health, Qatar University, Doha, Qatar., C GPD; Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore-632014, Tamil Nadu, India. georgepriyadoss@vit.ac.in.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2024 May 10; Vol. 24 (1), pp. 483. Date of Electronic Publication: 2024 May 10.
DOI: 10.1186/s12879-024-09332-x
Abstrakt: Background: Monkeypox (Mpox) is an important human pathogen without etiological treatment. A viral-host interactome study may advance our understanding of molecular pathogenesis and lead to the discovery of suitable therapeutic targets.
Methods: GEO Expression datasets characterizing mRNA profile changes in different host responses to poxviruses were analyzed for shared pathway identification, and then, the Protein-protein interaction (PPI) maps were built. The viral gene expression datasets of Monkeypox virus (MPXV) and Vaccinia virus (VACV) were used to identify the significant viral genes and further investigated for their binding to the library of targeting molecules.
Results: Infection with MPXV interferes with various cellular pathways, including interleukin and MAPK signaling. While most host differentially expressed genes (DEGs) are predominantly downregulated upon infection, marked enrichments in histone modifiers and immune-related genes were observed. PPI analysis revealed a set of novel virus-specific protein interactions for the genes in the above functional clusters. The viral DEGs exhibited variable expression patterns in 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 based on their histone-regulating and immunosuppressive properties. In the computational docking and Molecular Dynamics (MD) experiments, these proteins were shown to bind the candidate small molecule S3I-201, which was further prioritized for lead development.
Results: MPXV circumvents cellular antiviral defenses by engaging histone modification and immune evasion strategies. C6R-derived protein K7 binding candidate molecule S3I-201 is a priority promising candidate for treating Mpox.
(© 2024. The Author(s).)
Databáze: MEDLINE
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