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Remdesivir Mode Of Action
1. Remdesivir is a monophosphoramidate nucleoside prodrug that undergoes intracellular metabolic conversion to its active metabolite nucleoside triphosphate (NTP).
2. The active metabolite of remdesivir (remdesivir triphosphate [remdesivir-TP] subsequently targets the machinery responsible for the replication of the viral RNA genome, a highly conserved element of the viral life cycle.
3. Viral RdRp is the target protein for the active metabolite remdesivir-TP. Remdesivir-TP acts as the substrate for RdRp where it competes with ATP for incorporation into new strands. Inhibition ofEBOV RdRp most probably results from delayed chain termination.
4. Passage through the cell membrane by remdesivir is facilitated by the prodrug component attached to the nucleoside core.
5. Upon entering the target cell, the pronucleotide undergoes further phosphorylation steps to become the active triphosphate metabolite that effectively inhibits viral RNA replication.
6. Delayed chain termination is caused by the following processes:
(i) misintegration of nucleoside triphosphate (NTP) into replicating RNA by RdRp,
(ii) prevention of further chain elongation after NTP plus 3 additional nucleosides, and
(iii) premature termination of RNA synthesis.
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