While the novel coronavirus has ground much of daily life to a halt, researchers around the world are working overtime to find solutions. Since January, structural biologists have been busy modeling the virus' vital proteins, which could lead to therapeutic breakthroughs. Now, these scientists' efforts are detailed in a feature article in Chemical & Engineering News, the weekly newsmagazine of the American Chemical Society.
As soon as the genomic sequence of SARS-CoV-2, the virus that causes the COVID-19 disease, was mapped, researchers were off to the races in synthesizing its proteins and determining their structures. Unlike the highly complex genome sequence encoded in human DNA, the new coronavirus has a much shorter sequence and stores its genetic information in a single strand of RNA, writes Senior Editor Laura Howes. The encoded proteins help the virus attach to human cells and replicate, and knowledge of their structures is necessary for developing small molecules and other therapeutics to disrupt the proteins. The first structural models were uploaded to the Protein Data Bank, an international database for 3D structural data of large biomolecules, within five weeks of the earliest reported cases of COVID-19.
When it came to discovering the protein structures of SARS-CoV-2, researchers with expertise in other coronaviruses had the advantage. Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are both similar to the novel coronavirus, which scientists used as a basis for identifying protein sequences and shapes. Advances in technology have also greatly helped structural biologists in this effort, especially when it comes to imaging the proteins. X-ray crystallography, a key tool in structural biology, is largely automated, allowing for rapid and accurate data gathering. However, X-ray crystallography doesn't work for every protein. The relatively new cryo-electron microscopy has emerged as a standout method for capturing the proteins in SARS-CoV-2, reconstructing an array of 2D images into a clear 3D model. With much progress made in a few short months, researchers have abundant information to work with, but they caution that a market-ready treatment or vaccine will take time.