Contents

Obeldesivir

Oral COVID-19 drug

Obeldesivir

Names
IUPAC name [(2R,3S,4R,5R)-5-(4-Aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methyl 2-methylpropanoate
Identifiers
CAS Number	2647441-36-7 N
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL4863829
ChemSpider	115037299
KEGG	D12776
PubChem CID	162513664
UNII	Q55KCM7PXB
InChI InChI=1S/C16H19N5O5/c1-8(2)15(24)25-5-10-12(22)13(23)16(6-17,26-10)11-4-3-9-14(18)19-7-20-21(9)11/h3-4,7-8,10,12-13,22-23H,5H2,1-2H3,(H2,18,19,20)/t10-,12-,13-,16+/m1/s1 Key: YIHPGVCWGSURHO-VSBTWAGUSA-N
SMILES CC(C)C(=O)OC[C@@H]1[C@H]([C@H]([C@](O1)(C#N)C2=CC=C3N2N=CN=C3N)O)O
Properties
Chemical formula	C16H19N5O5
Molar mass	361.358 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Obeldesivir (GS-5245, ATV006) is an isobutyric ester prodrugofGS-441524 made by Gilead Sciences that is currently in Phase III trials for the outpatient treatment of COVID-19 in high risk patients.^[1][2] The purpose of the isobutyric ester modification on obeldesivir is to improve the oral bioavailability of the parent nucleoside, GS-441524. Obeldesivir is hydrolyzed to its parent nucleoside, GS-441524, which is in turn converted to remdesivir-triphosphate (GS-443902) by a nucleoside kinase, adenylate kinase and nucleotide diphosphate kinase.^[3][4]

GS-443902 is a bioactive ATP analogue with broad-spectrum antiviral activity ^[5] and is the same compound formed by remdesivir, though by a different enzymatic pathway. Unlike remdesivir, which is metabolized by enzymes that are highly expressed in the liver, GS-441524 released by obeldesivir is metabolized by enzymes that are evenly expressed throughout the body. Due to their different metabolic pathways, obeldesivir can be administered orally, whereas remdesivir must be administered intravenously for COVID-19 treatment.^{[citation needed]}

The pharmacokinetic properties of obeldesivir and improved was first published by Chinese researchers in May 2022. The Chinese group pursued investigation of obeldesivir independently from Gilead Sciences. Compared to IV administered GS-441524 in rats at 5 mg/kg, orally administered obeldesivir at 25 mg/kg (referred to as "ATV006") yielded approximately 22% bioavailability.^[6] Treatment with obdeldesivir reduced viral load and prevents lung pathology in KI-hACE2 and Ad5-hACE2 mouse models of SARS-CoV-2. A patent filed by Gilead Sciences with a priority date of August 27, 2020,^[7] found the bioavailability of GS-441524 after oral administration of obdeldesivir (compound 15) in mice, rats, ferrets, dogs, and cynomolgus macaques to be 41%, 63.9%, 154%, 94%, and 38%, respectively. Across all species evaluated, obeldesivir showed improved oral bioavailability compared to oral administration of the parent nucleoside, GS-441524.^{[citation needed]}

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