Evaluating cepharanthine analogues as natural drugs against SARS‐CoV‐2
Atsushi Hijikata,
Clara Shionyu‐Mitsuyama,
Setsu Nakae,
Masafumi Shionyu,
Motonori Ota,
Shigehiko Kanaya,
Takatsugu Hirokawa,
Shogo Nakajima,
Koichi Watashi,
Tsuyoshi Shirai
Affiliations
Atsushi Hijikata
Faculty of Bioscience Nagahama Institute of Bio‐Science and Technology Japan
Clara Shionyu‐Mitsuyama
Faculty of Bioscience Nagahama Institute of Bio‐Science and Technology Japan
Setsu Nakae
Faculty of Bioscience Nagahama Institute of Bio‐Science and Technology Japan
Masafumi Shionyu
Faculty of Bioscience Nagahama Institute of Bio‐Science and Technology Japan
Motonori Ota
Department of Complex Systems Science Graduate School of Informatics Nagoya University Japan
Shigehiko Kanaya
Computational Biology Laboratory Division of Information Science Graduate School of Science and Technology Nara Institute of Science and Technology (NAIST) Ikoma Japan
Takatsugu Hirokawa
Division of Biomedical Science Faculty of Medicine University of Tsukuba Japan
Shogo Nakajima
Department of Virology II National Institute of Infectious Diseases Shinjuku‐ku Japan
Koichi Watashi
Department of Virology II National Institute of Infectious Diseases Shinjuku‐ku Japan
Tsuyoshi Shirai
Faculty of Bioscience Nagahama Institute of Bio‐Science and Technology Japan
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.
