After more than two years of dealing with and adapting to life with COVID-19, the virus that causes this disease is still with us. And it looks set to be with us long into the future. Despite the use of vaccines and antiviral treatments, people are still suffering and even dying from serious COVID infection.
In addition, millions of people in poorer countries have not yet received access to vaccines, making them more susceptible to the effects of serious COVID. With this in mind, any effective treatment that may increase the chances of surviving severe infection is a high priority.
One area of interest has been the use of nanobodies, or miniature antibodies. Nanobodies are like small fragments of an antibody that bind only to a specific section (domain) of an antigen, such as the spike protein. They can immobilize a virus in this way, with their small and nimble structure making them able to get into folds and crannies in a viral spike protein. Nanobodies are produced in members of the camel family, including llamas, alpacas and camels, in response to infection by the SARS-CoV-2 virus.
Researchers at the Karolinska Institutet in Sweden have recently developed a novel strategy for identifying potent nanobodies from alpacas, in particular, that are effective against emerging SARS-CoV-2 variants. They have identified multiple different nanobodies and tested them in cell cultures, and in live mice, to find out whether they blocked infection by different variants of the SARS-CoV-2 virus. The findings are reported in two publications – one in the recent past in Nature Communications and the other, today, in Science Advances.
“With the help of advanced laboratory techniques, we were able to identify a panel of nanobodies that very effectively neutralized several variants of SARS-CoV-2,” said Professor Gerald McInerney, joint senior author of both studies.
Despite the roll-out of vaccines and antivirals, people in many countries still don’t have the access to COVID treatments that they need. Nanobodies from alpacas can be adapted for use in humans and carry several advantages over conventional treatments and antibodies. For example, they are cheap to produce on a mass scale and have favorable biochemical properties that make them effective in the treatment of different viruses.
The first report in Nature Communications describes a single nanobody, Fu2 (named after the alpaca Funny), that significantly reduced the viral load of SARS-CoV-2 in cell cultures and live mice. Using electron cryo-microscopy, the researchers found that Fu2 binds to two separate sites on the viral spike protein, thus inhibiting the virus’ ability to enter the host cells. This part of the study was conducted in collaboration with Hrishikesh Das and Martin Hällberg at the Department of Cell and Molecular Biology at Karolinska Institutet.
In the next phase of the study, the researchers combined a range of advanced laboratory techniques and computational methods, to assess the diversity of alpaca nanobodies and find out whether they would be effective against different variants of the SARS-CoV-2 virus. The results, presented today in Science Advances, revealed several additional nanobodies that effectively neutralized both the initial and beta variant of SARS-CoV-2 and even the more distantly related SARS-CoV-1.
“These nanobodies represent promising therapeutic candidates against several SARS-CoV-2 variants,” said study first author Leo Hanke, a postdoctoral researcher who established the nanobody technology in the McInerney group.
The researchers are currently applying the same techniques to identify which nanobodies from this set are best able to neutralize omicron, the variant of SARS-CoV-2 that is currently dominant in many countries worldwide.
“Once established, these libraries can be expanded and mined for nanobodies that neutralize new emerging variants,” said Professor Ben Murrell, also joint senior author of both studies.