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 causative pathogen, severe acute respiratory syndrome 2 (SARS-CoV-2), and also other pathogenic coronaviruses. In this study, we report a kind of bisbenzylisoquinoline alkaloid, neferine, as pan-coronavirus entry inhibitor. Neferine effectively protected HEK293/hACE2 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 (EC50) 0.13–0.41 ?M. blocked host calcium channels, thus inhibiting Ca2+-dependent membrane fusion suppressing virus entry. This study provides experimental data support fact that neferine may be promising lead for pan-coronaviruses therapeutic drug development.