Uses
GS-621763 is an orally available precursor to GS-441524 that exhibits anti-SARS-CoV-2 viral activity in mice. GS-621763 reduces viral load to undetectable levels in ferrets infected with SARS-CoV-2[1][2].
Biological Activity
GS-621763 is an orally bioavailable analog of remdesivir, which is efficiently converted in plasma to active metabolite GS-441524, or in lungs to the bioactive triphosphate GS-443902. GS-621763 effectively reduces SARS-CoV-2 burden to near-undetectable levels in ferrets.
in vivo
GS-621763 (30 and 60 mg/kg p.o., twice daily for 4 days) shows potent antiviral activity in SARS-CoV-2 infected BALB/c mouse model[1].
GS-621763 (10 mg/kg, p.o., twice daily for 4 days) shows significant antiviral activity in SARS-CoV-2-infected ferret model[2].
| Animal Model: | SARS-CoV-2 infected BALB/c mouse model[1] |
| Dosage: | 30 mg/kg and 60 mg/kg |
| Administration: | Oral gavage (p.o.), twice daily for 4 days |
| Result: | Significantly reduced lung infectious virus levels (30 mg/kg);
Further reduced ung infectious virus levels (60 mg/kg). |
| Animal Model: | SARS-CoV-2-infected ferret model[2] |
| Dosage: | 10 mg/kg |
| Administration: | Oral gavage (p.o.), twice daily for 4 days |
| Result: | Significantly reduced SARS-CoV-2 shedding, with virus undetectable in nasal lavages. |
References
[1] Schfer A, et al. Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice. bioRxiv [Preprint]. 2021 Sep 17:2021.09.13.460111. DOI:
10.1101/2021.09.13.460111[2] Cox RM, et al. Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets. Nat Commun. 2021 Nov 5;12(1):6415. DOI:
10.1038/s41467-021-26760-4
![D-Altrononitrile, 2-C-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2,5-anhydro-, 3,4,6-tris(2-methylpropanoate) Structure](https://www.chemicalbook.com/CAS/20211123/GIF/2647442-13-3.gif)