GC376 is a broad-spectrum

antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do ...

under development by the

biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...

company Anivive Lifesciences for therapeutic uses in humans and animals. Anivive licensed the exclusive worldwide patent rights to GC376 from

Kansas State University Kansas State University (KSU, Kansas State, or K-State) is a public land-grant research university with its main campus in Manhattan, Kansas, United States. It was opened as the state's land-grant college in 1863 and was the first public instit ...

. As of 2020, GC376 is being investigated as treatment for

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...

. GC376 shows activity against many human and animal viruses including

coronavirus Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the com ...

and

norovirus Norovirus, sometimes referred to as the winter vomiting disease, is the most common cause of gastroenteritis. Infection is characterized by non-bloody diarrhea, vomiting, and stomach pain. Fever or headaches may also occur. Symptoms usually deve ...

; the most extensive research has been multiple ''in vivo'' studies in cats treating a coronavirus which causes deadly feline infectious peritonitis. Other research supports use in

porcine epidemic diarrhea virus ''Porcine epidemic diarrhea virus'' (PED virus or PEDV) is a coronavirus that infects the cells lining the small intestine of a pig, causing porcine epidemic diarrhoea, a condition of severe diarrhea and dehydration. Older hogs mostly get sick ...

COVID-19

Since GC376 shows broad-spectrum activity against coronavirus, early on during the pandemic of 2020 it was suggested as a potential treatment for COVID-19. In response to the crisis, researchers at the

University of Arizona The University of Arizona (Arizona, U of A, UArizona, or UA) is a public land-grant research university in Tucson, Arizona. Founded in 1885 by the 13th Arizona Territorial Legislature, it was the first university in the Arizona Territory. T ...

published ''in vitro'' research indicating GC376 is highly active against 3CLpro in

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...

(the coronavirus which causes COVID-19). Another group of virologists at the

University of Alberta The University of Alberta, also known as U of A or UAlberta, is a public research university located in Edmonton, Alberta, Canada. It was founded in 1908 by Alexander Cameron Rutherford,"A Gentleman of Strathcona – Alexander Cameron Rutherfor ...

lead by

D. Lorne Tyrrell David Lorne John Tyrrell (born 1943) is a Canadian physician. Overview Born on February 10, 1943, in Edmonton, Alberta, he grew up on the family farm near Duffield and studied at the University of Alberta. Tyrrell interned at the University o ...

then released a separate publication confirming GC376's activity against 3CLpro in SARS-CoV-2 and also indicating GC376 had a potent antiviral effect. The next day,

Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...

's Zuckerman Institute hosted a COVID-19 Virtual Symposium which released research led by David Ho and characterized GC376 as "the most promising" protease inhibitor under investigation in Ho's lab because GC376 was the "most potent" and reached "complete viral inhibition" in a culture of cells infected with SARS-CoV-2.

Pharmacology

Pharmacodynamics

GC376 is a protease inhibitor. It blocks the 3CLpro, a protease common to many (+)ssRNA viruses, thereby preventing the viral

polyprotein Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

from maturing into its functional parts. Chemically, GC376 is the bisulfite adduct of an aldehyde GC373 and it behaves as a

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

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.

References

External links

Anivive Pharmaceuticals
Antiviral drugs SARS-CoV-2 main protease inhibitors {{antiinfective-drug-stub

COVID-19

Pharmacology

Pharmacodynamics

See also

References

External links