GC376

GC376 is a broad-spectrum antiviral medication under development by the biopharmaceutical company Anivive Lifesciences for therapeutic uses in humans and animals.^[1] Anivive licensed the exclusive worldwide patent rights to GC376 from Kansas State University.^[2] As of 2020, GC376 is being investigated as a treatment for COVID-19.^[3] GC376 shows activity against many human and animal viruses, including coronavirus and norovirus;^[4] the most extensive research has been multiple in vivo studies in cats treating a coronavirus, which causes deadly feline infectious peritonitis.^[5] Other research supports use in porcine epidemic diarrhea virus.^[6]

GC376

Legal status
Legal status	US: Investigational drug
Identifiers
IUPAC name sodium (2S)-1-hydroxy-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-(2-oxopyrrolidin-3-yl)propane-1-sulfonate
CAS Number	1416992-39-6 Y
PubChem CID	71481119
ChemSpider	29396096
UNII	H1NMJ5XDG5
ChEMBL	ChEMBL2315036
Chemical and physical data
Formula	C21H30N3NaO8S
Molar mass	507.53 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)C[C@@H](C(=O)N[C@@H](CC1CCNC1=O)C(O)S(=O)(=O)[O-])NC(=O)OCC2=CC=CC=C2.[Na+]
InChI InChI=1S/C21H31N3O8S.Na/c1-13(2)10-16(24-21(28)32-12-14-6-4-3-5-7-14)19(26)23-17(20(27)33(29,30)31)11-15-8-9-22-18(15)25;/h3-7,13,15-17,20,27H,8-12H2,1-2H3,(H,22,25)(H,23,26)(H,24,28)(H,29,30,31);/q;+1/p-1/t15?,16-,17-,20?;/m0./s1 Key:BSPJDKCMFIPBAW-JPBGFCRCSA-M

COVID-19

Crystal structure of the PEDV 3CLpro in complex with GC376.^[6]

Since GC376 shows broad-spectrum activity against coronavirus,^[7] early on during the pandemic of 2020, it was suggested as a potential treatment for COVID-19.^[8] In response to the crisis, researchers at the University of Arizona published in vitro research indicating GC376 is highly active against 3CLpro in SARS-CoV-2 (the coronavirus which causes COVID-19).^[9] Another group of virologists at the University of Alberta led by D. Lorne Tyrrell then released a separate publication confirming GC376's activity against 3CLpro in SARS-CoV-2 and also indicating GC376 had a potent antiviral effect.

Pharmacology

Pharmacodynamics

GC376 is a protease inhibitor. It blocks 3CLpro, a protease common to many (+)ssRNA viruses, thereby preventing the viral polyprotein from maturing into its functional parts. Chemically, GC376 is the bisulfite adduct of the aldehyde GC373, and it behaves as a prodrug for that compound. This aldehyde forms a covalent bond with the cysteine-144 residue at the protease's active site, giving a monothioacetal and blocking the enzyme's normal function.^[6][10]

See also

• 3CLpro-1
• Carmofur
• Ebselen
• GRL-0617
• Rupintrivir
• Theaflavin digallate
• Paxlovid