Inhibitory effect on SARS‐CoV‐2 infection of neferine by blocking Ca<sup>2+</sup>‐dependent membrane fusion
Yang Yang, Peng Yang, Cong Huang, Yuming Wu, Zhe Zhou, Xuejun Wang, Shengqi Wang
Abstract
Abstract The coronavirus disease 2019 (COVID‐19) pandemic has focused attention on the need to develop effective therapeutics against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), and also against other pathogenic coronaviruses. In this study, we report on a kind of bisbenzylisoquinoline alkaloid, neferine, as a pan‐coronavirus entry inhibitor. Neferine effectively protected HEK293/hACE2 and HuH7 cell lines from infection by different coronaviruses pseudovirus particles (SARS‐CoV‐2, SARS‐CoV‐2 [D614G, N501Y/D614G, 501Y.V1, 501Y.V2, 501Y.V3 variants], SARS‐CoV, MERS‐CoV) in vitro, with median effect concentration (EC 50 ) of 0.13–0.41 μM. Neferine blocked host calcium channels, thus inhibiting Ca 2+ ‐dependent membrane fusion and suppressing virus entry. This study provides experimental data to support the fact that neferine may be a promising lead for pan‐coronaviruses therapeutic drug development.