4.7 Article

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

期刊

JOURNAL OF MEDICAL VIROLOGY
卷 93, 期 10, 页码 5825-5832

出版社

WILEY
DOI: 10.1002/jmv.27117

关键词

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

类别

资金

  1. National Key Research and Development Program of China [2018YFA0900800]
  2. National Natural Science Foundation of China [81830101]
  3. National Science and Technology Major Project of China [2018ZX10305410-003-001]
  4. Beijing Nova Program [Z171100001117119]

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The study found that neferine effectively inhibits infection by various coronaviruses by blocking host calcium channels, thus showing potential as a promising lead for pan-coronaviruses therapeutic drug development.
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 mu M. 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.

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