A natural food preservative peptide nisin can interact with the SARS-CoV-2 spike protein receptor human ACE2

Virology. 2021 Jan 2:552:107-111. doi: 10.1016/j.virol.2020.10.002. Epub 2020 Oct 28.


Nisin, a food-grade antimicrobial peptide produced by lactic acid bacteria has been examined for its probable interaction with the human ACE2 (hACE2) receptor, the site where spike protein of SARS-CoV-2 binds. Among the eight nisin variants examined, nisin H, nisin Z, nisin U and nisin A showed a significant binding affinity towards hACE2, higher than that of the RBD (receptor binding domain) of the SARS-CoV-2 spike protein. The molecular interaction of nisin with hACE2 was investigated by homology modeling and docking studies. Further, binding efficiency of the most potent nisin H was evaluated through the interaction of hACE2:nisin H complex with RBD (receptor-binding domain) of SARS-CoV-2 and that of hACE2:RBD complex with nisin H. Here, nisin H acted as a potential competitor of RBD to access the hACE2 receptor. The study unravels for the first time that a globally used food preservative, nisin has the potential to bind to hACE2.

Keywords: COVID-19; Human ACE2 receptor; Molecular docking; Nisin; SARS-CoV-2; Therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Binding Sites
  • Humans
  • Models, Molecular
  • Molecular Docking Simulation
  • Nisin / chemistry
  • Nisin / metabolism*
  • Protein Binding
  • Protein Domains
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism*
  • Sequence Alignment
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*


  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Nisin
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2