Going Viral

Studying the biological replication of COVID-19 has become a topic of intense research within several academic and industrial laboratories across the world. The idea being that if science can understand how the coronavirus multiplies then it would inversely figure out how to stop it from doing so. The key to blocking the replication mechanism of COVID-19 could be found in an unsuspecting animal native to South America, the llama.

Associate Professor of Biology Piergiorgio Percipalle and Visiting Professor of Chemistry Gennaro Esposito are investigating the mechanism of COVID-19 replication and how certain non-structural viral proteins, by which viruses replicate, affect host cell function after infection.

Viruses, being non-living, do not have the means to replicate on their own. In order to do so, viruses depend on the host cell’s metabolism and energy to multiply within patients. That process produces non-structural viral proteins, components of a virus that are produced by using host cell functionality to replicate. The researchers have identified a specific non-structural virus protein, NSP-9, as essential to the viral replication. 

The researchers have cloned the NSP-9 viral protein and used the material to generate “a tool against the virus’s replication.”

“The tool is the nanobody, which is nothing more than a small version of an antibody that is obtained by injecting the NSP-9 protein into a host animal, in particular camelids,” Percipalle said.

Camelids are a large biological family that includes camels, alpacas, and llamas, the animal of choice in this research. This family of animals possesses a unique biological attribute that allows them to make relatively simple antibodies in response to viruses and other external challenges. The simple structure of these single chain antibodies is very specific, smaller in size, and more manageable. 

The team is isolating nanobodies now from the immunized llamas to identify the strongest candidate that can be used for the screening of COVID-19 patients’ samples that could change the way populations get tested.

Viral Therapy

The second function of characterizing these nanobodies is to identify a nanobody that potentially serves as a selective antiviral agent for COVID-19 treatment. If the experiments work out, then the nanobody becomes a potential antiviral drug.

The way nanobodies may inhibit the function of replication of COVID-19 would be by the creation of complexes that target proteins. By forming a complex that targets NSP-9 the nanobody compromises the viral protein’s mechanism that leads to the replication of the virus in the cellular context.

Once the researchers finalize the characterization process, they will test whether this nanobody, once introduced into the cell, can block viral protein and interfere with the replication of the virus.

“Antibodies are very complex molecules that are liable to environmental conditions such as temperature. Antibody preparations often require that you store them at minus 80 degrees Celsius and once unfrozen they must immediately be used. Whereas a nanobody is much more robust and easier to handle as a drug,” Esposito said.

Furthermore, nanobody production would be easier and cheaper than antibody production. The corresponding gene can be expressed by bacteria through a process called recombinant DNA technology. If the team is successful in developing an effective nanobody as a therapy against COVID-19, the potential drug that comes out of the research could more easily be transported and administered around the world.