Cyclin-dependent kinase 7 (CDK7) (CDK7)

This target refers to the host cell enzymatic machinery responsible for the phosphorylation of the Serine 5 (Ser5) residue within the C-terminal domain (CTD) of RNA polymerase II (Pol II). The central component of this machinery is Cyclin-dependent kinase 7 (CDK7), which functions as the catalytic subunit of the general transcription factor II H (TFIIH) complex. Serine 5 phosphorylation is a prerequisite for the transition of Pol II from the initiation phase to the elongation phase and is critical for the recruitment of mRNA capping enzymes. Many DNA viruses, including Herpes Simplex Virus Type 1 (HSV-1), hijack these host factors to facilitate their own gene expression and replication. Recent research has highlighted that specific phloroglucinol derivatives, such as those isolated from Rhodomyrtus tomentosa, can inhibit viral replication by blocking these host factors, thereby preventing the expression of the transcriptionally active Ser5-phosphorylated form of RNA polymerase. Targeting this host-dependency represents a novel antiviral strategy that may overcome resistance to standard nucleoside analogues, although it carries risks of systemic toxicity due to the inhibition of essential cellular transcription and cell cycle progression.

Other names

Host cell factors involved in serine 5-phosphorylated RNA polymerase expressionRNA polymerase II C-terminal domain Serine 5 kinaseCDK-activating kinase (CAK)TFIIH subunit CDK7Cyclin-dependent kinase 7

Inhibition of the CDK7 kinase activity within the TFIIH complex, which prevents the phosphorylation of the Serine 5 residue on the C-terminal domain of RNA polymerase II, thereby blocking the transition from transcription initiation to elongation and arresting the expression of viral and host genes.