In 2016, Dartmouth Ph.D. candidate Daniel Wrapp began working with llama antibodies to study two coronaviruses: SARS-CoV-1 and MERS-CoV. It was basic research for the McLellan Lab, which focuses on the proteins behind bacteria, fungi, parasites and viruses. Little did Wrapp know then that his basic research would have translational implications a lot sooner than expected.
Thanks to years of coronavirus research, Wrapp and his team have engineered a new antibody that binds tightly to a key protein on SARS-CoV-2, which causes COVID-19. They are already conducting preclinical studies in hamsters and, if everything goes well, the antibody treatment could potentially be available for human use in one year. Given the length of vaccine and drug development, it’s a promising timeline.
In order to reach to the key findings, there were two sets of research conducted classified as old and new research. When the immune system of camelids, such as llamas, alpacas and camels, detect foreign invaders, the animals produce two types of antibodies: one that is strikingly similar to human antibodies, and another that is more than half the size, known as single-domain antibodies.
“This reduced size gives single-domain antibodies some interesting properties that potentially make them valuable therapeutic candidates,” Wrapp explained to Laboratory Equipment. In the initial research conducted four years ago, the scientists focused on spike proteins, which allow the virus to both attach to and enter host cells, beginning the process of infection. While in cell culture, one antibody showed promise in stopping a coronavirus that relies on spike proteins from SARS-CoV-1.
A new antibody was devised by Wrapp and his entire team in their ongoing study, which was effective against SARS-CoV-2. This was done by figuring out the llama’s antibody that initially functioned against the SARS virus and by further linking the two copies of the same. The single-domain antibody that the researchers isolated was found to bind to the spike protein that covers the surface of SARS-CoV-2.
“The binding of this antibody to spike is able to prevent attachment and entry, which effectively neutralizes the virus. This single-domain antibody is particularly interesting because it binds to a conserved patch on the spike protein, meaning that it is capable of neutralizing both SARS-CoV-1 and SARS-CoV-2,” Wrapp said.
