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KMID : 0545120230330060788
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Journal of Microbiology and Biotechnology
2023 Volume.33 No. 6 p.788 ~ p.796
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Characterization of Natural Compounds as Inhibitors of NS1 Endonuclease from Canine Parvovirus Type 2
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Kwak So-Hyung
Kim Ha-Yeong
Yun Hye-Li
Lim Ju-Ho
Kang Dong-Hyun
Kim Do-Man
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Abstract
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Canine parvovirus type 2 (CPV-2) has high morbidity and mortality rates in canines. Nonstructural protein 1 (NS1) of CPV-2 has endonuclease activity, initiates viral DNA replication, and is highly conserved. Thus, it is a promising target for antiviral inhibitor development. We overexpressed a 41.9 kDa active recombinant endonuclease in Escherichia coli and designed a nicking assay using carboxyfluorescein and quencher-linked ssDNA as substrates. The optimal temperature and pH of the endonuclease were 37°C and pH 7, respectively. Curcumin, bisdemethoxycurcumin, demethoxycurcumin, linoleic acid, tannic acid, and α-tocopherol inhibited CPV-2 NS1 endonuclease with IC50 values of 0.29 to 8.03 μM. The extracted turmeric, yerba mate, and sesame cake suppressed CPV-2 NS1 endonuclease with IC50 values of 1.48, 7.09, and 52.67 μg/ml, respectively. The binding affinity between curcumin, the strongest inhibitor, and CPV-2 NS1 endonuclease by molecular docking was ?6.4 kcal/mol. Curcumin inhibited CPV-2 NS1 endonuclease via numerous hydrophobic interactions and two hydrogen bonds with Lys97 and Pro111 in the allosteric site. These results suggest that adding curcuminoids, linoleic acid, tannic acid, α-tocopherol, extracted turmeric, sesame cake, and yerba to the diet could prevent CPV-2 infection.
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KEYWORD
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Canine parvovirus 2, curcuminoids, endonuclease, sesame cake, turmeric, yerba mate
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