Inhibitory effect on SARS‐CoV‐2 infection of neferine by blocking Ca 2+ ‐dependent membrane fusion

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.