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Polygalic acid inhibits african swine fever virus polymerase activity: findings from machine learning and in vitro testing

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Abstract

African swine fever virus (ASFV), an extremely contagious virus with high mortality rates, causes severe hemorrhagic viral disease in both domestic and wild pigs. Fortunately, ASFV cannot be transmitted from pigs to humans. However, ongoing ASFV outbreaks could have severe economic consequences for global food security. Although ASFV was discovered several years ago, no vaccines or treatments are commercially available yet; therefore, the identification of new anti-ASFV drugs is urgently warranted. Using molecular docking and machine learning, we have previously identified pentagastrin, cangrelor, and fostamatinib as potential antiviral drugs against ASFV. Here, using machine learning combined with docking simulations, we identified natural products with a high affinity for AsfvPolX proteins. We selected five natural products (NPs) that are located close in chemical space to the six known natural flavonoids that possess anti-ASFV activity. Polygalic acid markedly reduced AsfvPolX polymerase activity in a dose-dependent manner. We propose an efficient protocol for identifying NPs as potential antiviral drugs by identifying chemical spaces containing high-affinity binders against ASFV in NP databases.

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Funding

This research was supported by grants from the National Research Foundation of Korea (NRF-2018R1D1A1B07050744 and NRF-2022R1A2B5B01001390) funded by the government of South Korea (MSIT).

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Authors and Affiliations

  1. College of Pharmacy, Dongduk Women’s University, Seoul, 02748, Republic of Korea

    Jiwon Choi, Hyundo Lee, Soyoung Cho & Yorim Choi

  2. Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, 54596, Republic of Korea

    Thuy X. Pham, Trang T. X. Huynh, Yun-Sook Lim & Soon B. Hwang

  3. Ilsong Institute of Life Science, Hallym University, Seoul, 07247, Republic of Korea

    Soon B. Hwang

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Contributions

Conceptualization, J.C. and Y.-S.L.; Methodology, software, and experiments, J.C., H.L., S.C., Y.C., T.P., T.X.P., and Y.-S.L.; Writing of the manuscript, J.C., H.L., S.C., Y.C., T.X.P., Y.-S.L., and Y.-S.L.; Review and editing, J.C., Y.-S.L. and S.B.H.; Project administration and supervision, J.C., Y.-S.L., and S.B.H. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jiwon Choi or Yun-Sook Lim.

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Choi, J., Lee, H., Cho, S. et al. Polygalic acid inhibits african swine fever virus polymerase activity: findings from machine learning and in vitro testing. J Comput Aided Mol Des 37, 453–461 (2023). https://doi.org/10.1007/s10822-023-00520-6

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