Inhibitory effect on SARS-CoV-2 infection of neferine by blocking Ca2+ -dependent membrane fusion

J Med Virol. 2021 Oct;93(10):5825-5832. doi: 10.1002/jmv.27117. Epub 2021 Jun 9.

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 (EC50 ) of 0.13-0.41 μM. Neferine blocked host calcium channels, thus inhibiting Ca2+ -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.

Keywords: Ca2+-dependency; SARS-CoV-2; entry inhibitor; membrane fusion; neferine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Benzylisoquinolines / pharmacology*
  • COVID-19 / virology
  • Calcium / metabolism*
  • Cell Line
  • Coronavirus / drug effects
  • Coronavirus / physiology
  • HEK293 Cells
  • Humans
  • Isoquinolines / pharmacology
  • Phenols / pharmacology
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / physiology
  • Virus Internalization / drug effects*

Substances

  • Antiviral Agents
  • Benzylisoquinolines
  • Isoquinolines
  • Phenols
  • isoliensinine
  • neferine
  • liensinine
  • Calcium