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The host transcriptional and translational machinery is the integrated system of enzymes and protein complexes responsible for the flow of genetic information from DNA to functional proteins. Transcription is primarily driven by RNA Polymerase II and associated transcription factors, while translation is executed by the 80S ribosome, transfer RNAs, and eukaryotic initiation factors (eIFs) (Alberts et al., Molecular Biology of the Cell). This machinery is a critical target in infectious diseases because viruses are obligate intracellular parasites that must hijack host ribosomes and translation factors to synthesize viral proteins (Stern-Ginossar et al., 2019, Nature Reviews Microbiology). In oncology, these pathways are frequently hyperactivated to support the rapid growth of malignant cells, leading to the development of drugs targeting the mTOR pathway and the eIF4F complex (Ruggero, 2013, Nature Reviews Cancer). However, because these processes are fundamental to the survival of all host cells, therapeutic intervention is often limited by significant systemic toxicity and a narrow therapeutic window (Butcher et al., 2006, Nature Chemical Biology).
Inhibition of DNA-dependent RNA polymerase, blockade of the ribosomal peptidyl transferase center, inhibition of eukaryotic initiation factors (e.g., eIF4A), and modulation of the mTORC1 signaling pathway to suppress mRNA translation and protein synthesis.
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