GS-443902 trisodium (GS-441524 triphosphate trisodium), the active triphosphate metabolite of Remdesivir (GS-5734), serves as a potent inhibitor of viral RNA-dependent RNA-polymerases (RdRp), displaying inhibitory concentrations (IC50) of 1.1 μM for RSV RdRp and 5 μM for HCV RdRp.

RdRp (RSV):1.1 µM (IC50), HCV RdRp:5 µM (IC50)

During a 72-hour incubation with 1 μM Remdesivir (GS-5734), levels of its metabolite, GS-443902 trisodium (GS-441524 triphosphate trisodium; Remdesivir metabolite trisodium), were monitored at intervals of 2, 24, 48, and 72 hours, showing peak concentrations (C max) of 300, 110, and 90 pmol/million cells in macrophages, HMVEC, and HeLa cell lines, respectively[1]. GS-443902 trisodium (compound 8a), a triphosphate (TP) derivative[2], impairs RSV RdRp-catalyzed RNA synthesis through integration into the nascent viral RNA, resulting in its premature termination. It is effectively transformed within cells to GS-443902 sodium, which selectively disrupts Ebola virus (EBOV) replication by targeting and inhibiting the viral RNA-dependent RNA polymerase (RdRp), thus blocking viral RNA synthesis[3].

Remdesivir (GS-5734; 10?mg?kg; i.v.) rapidly distributes into peripheral blood mononuclear cells (PBMCs), and efficient conversion to GS-443902 trisodium (Remdesivir metabolite trisodium; NTP) is apparent within 2?h of dose administration in rhesus monkeys. In PBMCs, GS-443902 trisodium represents the predominant metabolite and is persistent with a t 1/2 of 14?h and levels required for >50% virus inhibition for 24?hours[3].