Evaluating cepharanthine analogues as natural drugs against SARS-CoV-2

  • FEBS Open Bio. 2022 Jan;12(1):285-294. doi: 10.1002/2211-5463.13337.
Atsushi Hijikata  1 ,  Clara Shionyu-Mitsuyama  1 ,  Setsu Nakae  1 ,  Masafumi Shionyu  1 ,  Motonori Ota  2 ,  Shigehiko Kanaya  3 ,  Takatsugu Hirokawa  4  5  6 ,  Shogo Nakajima  7 ,  Koichi Watashi  7  8  9 ,  Tsuyoshi Shirai  1
Affiliations
  • 1. Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Japan.
  • 2. Department of Complex Systems Science, Graduate School of Informatics, Nagoya University, Japan.
  • 3. Computational Biology Laboratory Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Ikoma, Japan.
  • 4. Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Japan.
  • 5. Transborder Medical Research Center, University of Tsukuba, Japan.
  • 6. Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
  • 7. Department of Virology II, National Institute of Infectious Diseases, Shinjuku-ku, Japan.
  • 8. Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Shinjuku-ku, Japan.
  • 9. Department of Applied Biological Sciences, Tokyo University of Science, Noda, Japan.
PMID: 34850606 DOI: 10.1002/2211-5463.13337
Abstract

Cepharanthine (CEP) is a natural biscoclaurine alkaloid of plant origin and was recently demonstrated to have anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) activity. In this study, we evaluated whether natural analogues of CEP may act as potential anti-coronavirus disease 2019 drugs. A total of 24 compounds resembling CEP were extracted from the KNApSAcK database, and their binding affinities to target proteins, including the spike protein and main protease of SARS-CoV-2, NPC1 and TPC2 in humans, were predicted via molecular docking simulations. Selected analogues were further evaluated by a cell-based SARS-CoV-2 Infection assay. In addition, the efficacies of CEP and its analogue tetrandrine were assessed. A comparison of the docking conformations of these compounds suggested that the diphenyl ester moiety of the molecules was a putative pharmacophore of the CEP analogues.

Keywords
SARS-CoV; coronavirus; drug repurposing; molecular docking; natural drug.
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