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
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.