Galidesivir triphosphate

Galidesivir triphosphate (Immucillin-A triphosphate) is converted by the prodrug Galidesivir. Galidesivir triphosphate is a substrate for viral RNA-dependent RNA polymerase (RDRP), resulting in termination of viral RNA replication and thus serves as an antiviral. Galidesivir triphosphate inhibits HCV NS5B RNA polymerase activity and protects mice against Ebola[1][2].

Research Areas >> Infection

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

In virus-infected cells, Galidesivir is converted to the triphosphate, is incorporated into the viral transcript, and functions as an atypical chain-terminator for RNA-dependent RNA polymerases. Galidesivir is converted to the mono-, di-, and triphosphates in virus-infected human Huh-7 cells[1]. Galidesivir triphosphate (Immucillin-A triphosphate) (1-60 μM) inhibits hepatitis C virus (HCV) RNA polymerase transcriptional activity in a cell-free, isolated enzyme transcription assay.The triphosphate is a substrate for viral RNA-dependent RNA polymerase. Its incorporation permits the addition of a few additional encoded bases at which point the Galidesivir-modified RNA cannot be elongated[2].

In vivo conversion of Galidesivir to its TP (Galidesivir triphosphate) nucleotide is particularly efficient[3]

[1]. Evans GB, et al. Immucillins in Infectious Diseases. ACS Infect Dis. 2018 Feb 9;4(2):107-117.

[2]. Warren TK, et al. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature. 2014 Apr 17;508(7496):402-5.

[3]. Taylor R, et al. BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease. J Infect Public Health. 2016 May-Jun;9(3):220-6.