Blocking Coronavirus from Entering Cells

Cornell University researchers set out to analyze the structure and characteristics of two coronaviruses—SARS-CoV and MERS-CoV—with a focus on the spike protein that allows these viruses to infect cells via the transferring of their genome. In doing so, they identified a possible target for antiviral treatment of COVID-19. Their study was published Monday in Antiviral Research.

Membrane fusion is a multistep process that plays a critical role in the spread of coronaviruses. The process begins with the virus recognizing that it has found the right type of cell to infect. To do this, the virus receives feedback from the chemical environment, including cues like the receptor that the host cell presents. The virus then attaches to the host cell receptor by way of the spike protein.

Next, a piece of the spike protein, called the fusion peptide, interacts directly with the host cell membrane and facilitates merging to form a fusion pore. The virus then transfers its genome into the host cell through this pore. These genomic instructions essentially commandeer the host’s machinery to produce more viruses.

The group found that calcium ions that interact with the fusion peptide can change the peptide’s structure as well as how it interacts with membranes in ways that promote infection in MERS and SARS. Now, the researchers are turning their attention to SARS-CoV-2 because the fusion peptides are consistent in all three viruses.

The team is hopeful that the research will help answer some of the chemistry-related questions surrounding COVID-19, such as how it was able to move into humans, what chemical cues facilitated that process, and why the virus is able to replicate so easily in the respiratory tract. The team’s findings have led to supplemental funding from the National Institutes of Health (NIH) through its Research Project Grant program to develop an antibody that could block the virus’s entry by interacting with the fusion peptide.