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Engineering Antiviral Agents via Surface Plasmon Resonance
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Engineering Antiviral Agents via Surface Plasmon Resonance

Published on: June 14, 2022

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

Yang Yang1, Peng Yang1,2, Cong Huang1,3

  • 1Beijing Institute of Radiation Medicine, Beijing, China.

Journal of Medical Virology
|June 1, 2021
PubMed

Insights

Neferine, a natural compound, acts as a broad-spectrum inhibitor against multiple coronaviruses, including SARS-CoV-2 variants. It blocks viral entry by inhibiting calcium channels, offering a potential therapeutic lead for pan-coronavirus infections.

Area of Science:

  • Virology
  • Pharmacology
  • Biochemistry

Background:

  • The COVID-19 pandemic highlights the urgent need for broad-spectrum antiviral therapeutics against SARS-CoV-2 and other coronaviruses.
  • Existing treatments often target specific viral strains, necessitating the development of pan-coronavirus strategies.

Purpose of the Study:

  • To investigate the potential of neferine, a bisbenzylisoquinoline alkaloid, as a pan-coronavirus entry inhibitor.
  • To evaluate neferine's efficacy against various authentic and pseudotyped coronavirus strains in vitro.

Main Methods:

  • Utilized HEK293/hACE2 and HuH7 cell lines for infection assays.
  • Tested neferine against pseudovirus particles of SARS-CoV-2 (including variants), SARS-CoV, and MERS-CoV.
  • Determined median effect concentration (EC50) values for neferine's antiviral activity.
  • Investigated the mechanism of action, focusing on host calcium channel blockade.

Main Results:

  • Neferine demonstrated potent in vitro inhibition of infection by SARS-CoV-2 (including D614G, N501Y/D614G, 501Y.V1, 501Y.V2, 501Y.V3 variants), SARS-CoV, and MERS-CoV.
  • The median effect concentration (EC50) ranged from 0.13 to 0.41 μM, indicating high potency.
  • Neferine was found to block host calcium channels, a mechanism crucial for inhibiting Ca2+-dependent membrane fusion and subsequent viral entry.

Conclusions:

  • Neferine exhibits broad-spectrum antiviral activity against multiple pathogenic coronaviruses by inhibiting viral entry.
  • The compound's mechanism involves the blockade of host calcium channels, disrupting the fusion process.
  • Neferine represents a promising lead compound for the development of novel pan-coronavirus therapeutics.
Keywords:
Ca2+-dependencySARS-CoV-2entry inhibitormembrane fusionneferine

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