A Duke University School of Medicine study in Molecular Cell provides the most detailed look yet at the SARS-CoV-2 Omicron XBB variants, which emerged in late 2022 and have evolved to remain infectious while evading the immune system.
As Omicron and its variants swept through local and global communities, they fine-tuned their spike proteins to tightly latch onto and infect cells, while making it harder for the virus to be recognized by the immune system. The XBB spike proteins also evolved to become more stable.
The study led by scientists in the Department of Biochemistry and Duke Human Vaccine Institute could influence the ongoing fight against COVID-19. The current COVID-19 vaccine booster incorporates an engineered version of the XBB 1.5 spike protein. By analyzing the structure and function of spike proteins, the Duke team has gained insights into the virus’ evolution and factors driving its adaptability.
Researchers used cryo-electron microscopy to solve the structures of these spike proteins, allowing for atomic-level visualization of their shape and function. This technique, which involves freezing proteins in solution and capturing hundreds of thousands of images with an electron microscope, enabled the researchers to reconstruct the 3-dimensional structures of the XBB lineage’s spike proteins.
“Even small changes in the protein structure could have significant effects on how the virus behaves,” said lead study author Ellie Zhang, a graduate student in the Department of Biochemistry.
The study also employed surface plasmon resonance and enzyme-linked immunosorbent essay (ELISA) to measure the proteins’ ability to bind antibodies, alongside differential scanning fluorimetry (DSF) to assess their stability.
“The atomic level details revealed in this research not only advance our understanding of how the virus continues to evolve but also provide crucial data that could inform the development of next-generation vaccines,” said senior study author Priyamvada Acharya, PhD, associate professor in biochemistry and member of Duke Human Vaccine Institute.