Researchers at Karolinska Institutet in Sweden have developed a new strategy to identify powerful miniature antibodies, called nanobodies, against emerging variants of SARS-CoV-2. The approach led to the discovery of several nanobodies that, in cell cultures and mice, effectively blocked infection by different variants of SARS-CoV-2. The results, which are described in the reviews Nature Communication and Scientists progresscould pave the way for new treatments for COVID-19.
“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,” says Gerald McInerney, professor in the Department of Microbiology, Tumor and Cell Biology (MTC ), Karolinska Institutet, and co-lead author of both studies.
Despite the deployment of vaccines and antivirals, the need for effective treatments for severe COVID-19 infections remains high. Nanobodies, which are antibody fragments that occur naturally in camelids and can be adapted to humans, are promising therapeutic candidates because they offer several advantages over conventional antibodies. For example, they have favorable biochemical properties and are easy to cost-effectively produce on a large scale.
In the now published studies, the labs of Gerald McInerney and Ben Murrell, also at MTC, identify several potent nanobodies derived from an alpaca immunized with SARS-CoV-2 antigens.
The first report in Nature Communication described a single nanobody, Fu2 (named after the alpaca Funny), that significantly reduced SARS-CoV-2 viral load in cell cultures and mice. Using cryo-electron microscopy, the researchers found that Fu2 naturally binds to two distinct sites on the viral spike, thereby inhibiting the ability of the virus to enter the host cell. This part of the study was conducted in collaboration with Hrishikesh Das and Martin Hällberg from the Department of Cellular and Molecular Biology at Karolinska Institutet.
The researchers then delved into the alpaca’s nanobody repertoire by combining a range of advanced laboratory techniques and computational methods, resulting in a detailed described library of nanobodies.
The results, presented in Scientists progressrevealed additional nanobodies that, in cell cultures and mice, effectively neutralized both the founder and beta variant of SARS-CoV-2 and even neutralized the more distant SARS-CoV-1.
“These nanobodies represent promising therapeutic candidates against several SARS-CoV-2 variants,” says first author Leo Hanke, a postdoctoral researcher who established the nanobody technology in the McInerney Group.
Researchers are currently applying the same techniques to identify which nanobodies from this set are best able to neutralize omicron, the now dominant variant of SARS-CoV-2.
“Once established, these libraries can be extended and exploited for nanobodies that neutralize newly emerging variants,” says Assistant Professor Ben Murrell, also co-lead author of both studies.
Researchers identify nanobody that can prevent COVID-19 infection
Leo Hanke et al, Bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo, Nature Communication (2022). DOI: 10.1038/s41467-021-27610-z
Leo Hanke et al, Multivariate exploration of an alpaca immune repertoire identifies potent cross-neutralizing SARS-CoV-2 nanobodies, Scientists progress (2022). DOI: 10.1126/sciadv.abm0220. www.science.org/doi/10.1126/sciadv.abm0220
Provided by Karolinska Institutet
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