Structure and Orientation of the SARS-Coronavirus-2 Spike Protein at Air-Water Interfaces

Mikkel Bregnhøj, Steven J. Roeters*, Adam S. Chatterley, Fani Madzharova, Rolf Mertig, Jan Skov Pedersen, Tobias Weidner*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


The SARS coronavirus 2 (SARS-CoV-2) spike protein is located at the outermost perimeter of the viral envelope and is the first component of the virus to make contact with surrounding interfaces. The stability of the spike protein when in contact with surfaces plays a deciding role for infection pathways and for the viability of the virus after surface contact. While cryo-EM structures of the spike protein have been solved with high resolution and structural studies in solution have provided information about the secondary and tertiary structures, only little is known about the folding when adsorbed to surfaces. We here report on the secondary structure and orientation of the S1 segment of the spike protein, which is often used as a model protein for in vitro studies of SARS-CoV-2, at the air-water interface using surface-sensitive vibrational sum-frequency generation (SFG) spectroscopy. The air-water interface plays an important role for SARS-CoV-2 when suspended in aerosol droplets, and it serves as a model system for hydrophobic surfaces in general. The SFG experiments show that the S1 segment of the spike protein remains folded at the air-water interface and predominantly binds in its monomeric state, while the combination of small-angle X-ray scattering and two-dimensional infrared spectroscopy measurements indicate that it forms hexamers with the same secondary structure in aqueous solution.

Original languageEnglish
JournalJournal of Physical Chemistry B
Pages (from-to)3425-3430
Number of pages6
Publication statusPublished - 12 May 2022


  • COVID-19
  • SARS-CoV-2
  • Humans
  • Spike Glycoprotein, Coronavirus/chemistry
  • Water/chemistry


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