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Broad-spectrum antiviral medication
GC376
Legal status
sodium (2S)-1-hydroxy-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-(2-oxopyrrolidin-3-yl)propane-1-sulfonate
CAS Number
PubChem
CID
ChemSpider
UNII
ChEMBL
Formula C 21 H 30 N 3 Na O 8 S
Molar mass 507.53 g·mol−1 3D model (
JSmol )
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=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
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 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]
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 the
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 an 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
References
^
"Anivive" . www.anivive.com . Retrieved 2020-05-14 .
^
"Anivive licenses antiviral drug for fatal cat disease" . www.k-state.edu . September 20, 2018. Retrieved 2020-05-14 .
^ Stockwell B (6 May 2020).
"COVID-19 Virtual Symposium" . Retrieved 2020-05-14 – via YouTube.
^ Takahashi D, Kim Y, Lovell S, Prakash O, Groutas WC, Chang KO (December 2013).
"Structural and inhibitor studies of norovirus 3C-like proteases" . Virus Research . 178 (2): 437–444.
doi :
10.1016/j.virusres.2013.09.008 .
PMC
3840063 .
PMID
24055466 .
^ Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, et al. (April 2018).
"Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis" . Journal of Feline Medicine and Surgery . 20 (4): 378–392.
doi :
10.1177/1098612X17729626 .
PMC
5871025 .
PMID
28901812 .
^
a
b
c Ye G, Wang X, Tong X, Shi Y, Fu ZF, Peng G (February 2020).
"Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376" . Viruses . 12 (2): 240.
doi :
10.3390/v12020240 .
PMC
7077318 .
PMID
32098094 .
^ Pillaiyar T, Meenakshisundaram S, Manickam M (April 2020).
"Recent discovery and development of inhibitors targeting coronaviruses" . Drug Discovery Today . 25 (4): 668–688.
doi :
10.1016/j.drudis.2020.01.015 .
PMC
7102522 .
PMID
32006468 .
^ Morse JS, Lalonde T, Xu S, Liu WR (March 2020).
"Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV" . ChemBioChem . 21 (5): 730–738.
doi :
10.1002/cbic.202000047 .
PMC
7162020 .
PMID
32022370 .
^ Ma C, Sacco MD, Hurst B, Townsend JA, Hu Y, Szeto T, et al. (January 2020).
"Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease" . bioRxiv .
doi :
10.1101/2020.04.20.051581 .
PMC
7263507 .
PMID
32511378 .
S2CID
216145410 .
^ Vuong W, Khan MB, Fischer C, Arutyunova E, Lamer T, Shields J, et al. (August 2020).
"Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication" . Nature Communications . 11 (1): 4282.
doi :
10.1038/s41467-020-18096-2 .
PMC
7453019 .
PMID
32855413 .
S2CID
218551888 .
External links