Inhibition of Replication of Adenovirus by 6-diazo-5-oxo-L-norleucine (DON)

Abstract

The antibiotic known as 6-diazo-5-oxo-L-norleucine (DON) inhibits the growth of several types of Gram-positive and Gram-negative bacteria. DON has also been demonstrated to inhibit the replication of poliovirus, respiratory syncytial virus, mumps, and herpes simplex virus in cultured eukaryotic cells. DON is an analogue of glutamine and inhibits the synthesis of glycoproteins and purine nucleotides in cells that are treated with the antibiotic. DON inhibits the aminotransferase enzyme that uses the amino group of glutamine to construct the precursor molecules of nucleotides and to convert fructose-6-phosphate into glucosamine for glycoprotein synthesis. DON does not inhibit the enzyme activity of Buffalo green monkey kidney (BGMK) cells at concentrations as high as 2,500 µg/ml. At a concentration of 5 µg/ml, DON inhibits the replication of adenovirus in BGMK cells by 71.7% and at a concentration of 10 µg/ml, DON inhibits the replication of adenovirus by 92%. Addition of excess glutamine and nucleosides partially reverses the inhibition of adenovirus replication by DON while the addition of excess glucosamine has no effect on the inhibition of virus replication by DON. These results suggest that DON inhibits the replication of adenovirus by inhibiting the metabolism of glutamine and nucleosides during adenovirus replication but not glycoprotein synthesis.

Keywords: 6-diazo-5-oxo-L-norleucine (DON), adenovirus, Buffalo Green Monkey Kidney (BGMK) cells

Cite this Article

Goldstein G, Harden JL. Inhibition of Replication of Adenovirus by 6-diazo-5-oxo-L-norleucine (DON). Research & Reviews: Journal of Microbiology and Virology. 2016; 6(3): 31–37p.