Antiviral used to Treat Coronavirus in Cats Effective on Humans

Biochemist Joanne Lemieux

Researchers at the University of Alberta have said that a drug used to treat deadly coronavirus infections in cats can potentially be an effective treatment against SARS-CoV-2. The results of the experiment published in the journal Nature Communications on August 27, 2020.

The study aided scientists at the U.S. Department of Energy’s SLAC National Accelerator Laboratory, paves the way for human clinical trials.

“This drug is very likely to work in humans, so we’re encouraged that it will be an effective treatment for COVID-19 patients,” said Joanne Lemieux, a professor of biochemistry at the University of Alberta and the study’s senior author.

GC376 works interfering with a virus’ ability to replicate in cats, thus ending the virus. Derivatives of the following drug were first studied in 2003 after the outbreak of severe acute respiratory syndrome (SARS). It was further developed veterinary researchers who showed it cures fatal feline affliction.

Visual Illustration of the Results of the Experiment

a Schematic representation of inhibitor prodrug GC376, used to treat cats of FIP, and GC373, the actual protease inhibitor.
b IC50 values for GC373 and GC376 for SARS-CoV-2 Mpro and
c SARS-CoV Mpro cleavage of Abz-SVTLQSG-Y(NO2)-R. N = 3, values are represented as mean ± SE.
a Apo-SARS-CoV-2 Mpro forms a dimer (6WTM.pdb).
b Prodrug GC376, when incubated with SARS-CoV-2 Mpro, converts to GC373 which forms a covalent bond with C145. Surface representation reveals the active site pocket in complex with GC373 (6WTJ.pdb).
c Ribbon representation of one SARS-CoV-2 protomer in complex with inhibitor GC373 binding in domain II.
d GC373 interacts covalently with the active site cysteine of SARS-CoV-2 Mpro. Electron density at 1σ is shown in gray mesh.
a GC373 forms a covalent bond with C145, and the oxyanion is stabilized backbone H-bonds with G143, S144, and C145. 
b The P2 position of GC373 is stabilized a hydrophobic pocket the general base H41, and residues M49, and M165. 
c, d H-bonds are established with GC373 and side chains of H163 and E166, as well as backbone of residue E166. SARS-CoV-2 Mpro is represented in cartoon representation with the inhibitor in pink. P1, P2, and P3 of the peptidyl inhibitor are indicated. PDB Code:6WTJ.
a, b SARS-CoV-2 growth in Vero E6 cells was determined plaque assays 48 h after infection in the presence of various concentrations of drug. Cytotoxicity was measured using the CellTiter-Glo assay.
a Percent inhibition of SARS-CoV-2 GC373 in Vero E6 cells (blue open circles) and cytotoxicity in Vero E6 (blue closed circles) and A549 cells (orange). 
b Percent inhibition of SARS-CoV-2 GC376 in Vero E6 cells (blue open circles) and cytotoxicity in Vero E6 (blue, closed circles) and A549 cells (orange). 
c, d To measure the reduction in virus yield, Vero E6 cells were infected with MOI = 0.01 of SARS-CoV-2 in triplicate without or with various concentration of GC373 
c or GC376 
d for 24 h and the supernatants harvested, RNA isolated and quantified qRT-PCR. In the EC50 curves, values are represented as mean ± SD of at least two independent experiments. For toxicity assay, values are represented as mean ± SD of 12 independent experiments. RNA data are presented as mean ± SD, with n = 3 independent experiments and individual data points shown.

(The above article has been written from inferences taken the Journal published in Nature Communications)

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