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

Autor: Clara Shionyu-Mitsuyama, Takatsugu Hirokawa, Atsushi Hijikata, Tsuyoshi Shirai, Setsu Nakae, Motonori Ota, Koichi Watashi, Masafumi Shionyu, Shogo Nakajima, Shigehiko Kanaya
Rok vydání: 2021
Předmět:
Popis: Cepharanthine is a natural of plant origin, and recently demonstrated to have anti-SARS-CoV-2 activity. In order to evaluate the other natural analogues as a potential COVID-19 drug, a total of 24 compounds resembling cepharanthine were extracted from the KNApSAcK database, and their binding affinities to supposed target proteins, namely, spike protein and main protease of SARS-CoV-2, NPC1, and TPC2, were predicted via molecular docking simulations. Selected analogues were further evaluated by a cell-based SARS-CoV-2 infection assay, and the efficacies of cepharanthine (IC50 1.90 uM) and tetrandrine (IC50 10.37 uM) were demonstrated. From a comparison of the docking conformations of these compounds, the diphenyl ester moiety of the molecules was suggested for a putative pharmacophore of the cepharanthine-analogues.
Databáze: OpenAIRE