Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Characterization of Natural Compounds as Inhibitors of NS1 Endonuclease from Canine Parvovirus Type 2

  • So-Hyung Kwak (Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University) ;
  • Hayeong Kim (The Institute of Food Industrialization, Institutes of Green Bio Science and Technology, Seoul National University) ;
  • Hyeli Yun (Graduate School of International Agricultural Technology, Seoul National University) ;
  • Juho Lim (Graduate School of International Agricultural Technology, Seoul National University) ;
  • Dong-Hyun Kang (Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University) ;
  • Doman Kim (The Institute of Food Industrialization, Institutes of Green Bio Science and Technology, Seoul National University)
  • Received : 2022.11.22
  • Accepted : 2023.01.30
  • Published : 2023.06.28
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Abstract

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℃ 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 ㎍/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.

Keywords

Acknowledgement

This study was supported by a grant from the National Research Foundation of Korea, Republic of Korea (2022R1I1A1A01069773) awarded to HY Kim, (2022R1F1A106343411) awarded to D Kim, and (2021R1A6A3A13042816) awarded to SH Kwak. This study was also funded by the Technology Innovation Program (20009663), the Ministry of Trade, Industry & Energy (MOTIE, Republic of Korea), and the OTTOGI Corporation, Republic of Korea, through the Research and Publication Project.

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