A close-up at COVID-19 coronavirus attacking the lungs

Understanding how a virus enters a host cell and the details surrounding how it binds to the receptor on the host cell is critical to facilitate the development of detection methods, antiviral therapeutics, and vaccines. Once this critical piece of information is solved, it can be utilized to target and combat the virus.

A team of researchers from the Westlake Institute for Advanced Study in Hangzhou, Westlake University and Tsinghua University has produced a high-resolution image of SARS-CoV-2 during the initial phase of infection of a human cell. In their paper published in the journal Science, the research team describes how they captured the image and what it showed.

The study built on recent work done by a combined team from the University of Texas at Austin and the National Institutes of Health. They found that a protein on the virus, known as its spike protein, was better able to bind to the ACE2 protein in humans than the virus responsible for the SARS outbreak in 2003.

As a way to learn more about how the virus binds, the researchers used cryo-electron microscopy to capture images of the ACE2 protein prior to infection and during initial stages of infection by a SARS-CoV-2 virus.

The ACE2 protein is an enzyme that plays a role in converting a hormone called angiotensin to an active state, allowing it to help constrict blood vessels and thus control blood pressure. It is found in the heart, intestines, kidneys, and most importantly for this new work, in the lungs. Prior work has shown that this protein is initially targeted by several viruses such as SARS. The reason it plays such a big a role in viral infections is because it also helps to transport amino acids across cell membranes.

To create the new images, the researchers produced a solution with a high concentration of the ACE2 protein and another with a high concentration of the protein and live viruses. They then froze the samples very quickly to keep them in place and fired electrons at them. The process resulted in the creation of multiple 2-D images, which they combined to form 3-D images.

Now, not even one month later, Qiang Zhou, PhD, from Westlake University in Zhejiang Province, China, presented cryo-EM structures of full-length human ACE2, in the presence of a neutral amino acid transporter B0AT1, with or without the RBD of the surface spike glycoprotein of SARS-CoV-2. The structures are at an overall resolution of 2.9 Å, with a local resolution of 3.5 Å at the ACE2-RBD interface.

The study is significant and marks an important step forward in understanding the virus’s entry into host cells. The findings not only shed light on the mechanistic understanding of viral infection, but will also facilitate development of viral detection techniques and potential antiviral therapeutics.