Coronavirus spike protein deteriorates during storage, but it can be restored

The spike protein critical for coronavirus research -- and for some COVID-19 vaccines -- slowly deteriorates while in storage, which can affect research results and vaccine production, a new study suggests. But the effect can be reversed.

The SARS-CoV-2 spike protein, which is used in laboratories around the world, is unstable under conventional storage conditions of neutral pH and 4 degrees Celsius, according to the study published in Journal of Biological Chemistry.

And methods typically used to monitor protein quality may not detect the gradual deterioration, said study coauthor Yaroslav Tsybovsky of the Frederick National Laboratory for Cancer Research (FNL). After about a month, the protein may no longer be effective.

“This obviously has important implications for research but also, potentially, for vaccine production and distribution because some protein-based vaccines rely on this or very similar type of spike,” Tsybovsky said.

But the deterioration can be reversed and altogether avoided. If the spike protein is briefly exposed to an acidic environment (pH 4.0-5.5), its structure will be restored, according to the study, which was led by Peter Kwong of the National Institute of Allergy and Infectious Diseases. And if the protein is stored in an acidic environment from the outset, the spike protein will maintain its integrity.

Tsybovsky and FNL’s Tyler Stephens contributed to the study by producing ultra-high-resolution structures of the virus spike protein using state-of-the-art cryogenic electron microscopy with data sets from the National Cryo-EM Facility at FNL.

For the imaging, virus spike samples were flash frozen in a very thin layer of water and then bombarded by electrons, which scattered in different directions. A sensor detected these directions, and computer processing translated this information into 3-D images at near atomic resolution. Tsybovsky and Stephens also studied the storage stability of the spike protein using negative-stain electron microscopy, which has a higher throughput but lower resolution.

The study highlights the importance of a thorough understanding of the biochemical characteristics of a viral protein, including details about its 3-D structure and stability over time, Tsybovsky said.