Researchers at Karolinska Institutet have developed a new strategy to identify potent miniature antibodies, so-called nanobodies, against emerging variants of SARS-CoV-2.
This approach led to the discovery of several nanobodies that in cell cultures and mice effectively blocked infection with different variants of SARS-CoV-2. The findings, which are described in the journals Nature Communications and Science Advances, could pave the way for new treatments against COVID-19.
"With the help of advanced laboratory techniques, we were able to identify a group of nanoparticles that effectively neutralized many variants of SARS-CoV-2," says Gerald McInerney, professor in the Department of Microbiology, Oncology, and Cell Biology (MTC). , Karolinska Institutet, and co-lead author of both studies.
Despite the proliferation of vaccines and antiviral drugs, the need for effective treatments against severe COVID-19 infection remains high. Nanobodies - parts of antibodies that occur naturally in camels 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 studies now published, the laboratories of Gerald McInerney and Ben Morell, also at MTC, have identified several robust alpaca-derived nanobodies immunized with SARS-CoV-2 antigens.
Reduced viral load
The first report in Nature Communications describes a single nanobody, Fu2 (named after alpaca Funny), which significantly reduced the viral load of SARS-CoV-2 in cell cultures and mice. Using electron microscopy, the researchers found that Fu2 naturally binds to two separate sites on the viral spike, inhibiting the virus's ability to enter the host cell. This part of the study was conducted in collaboration with Hrishikesh Das and Martin Hällberg in the Department of Cell and Molecular Biology at Karolinska Institutet.
Next, the researchers delved into the repertoire of alpaca nanobodies by combining a combination of advanced laboratory techniques and computational methods, resulting in a library of nanobodies described in detail.
The results, presented in Science Advances, revealed the presence of additional nanobodies in cell cultures and mice that effectively neutralized both the founder and beta variant of SARS-CoV-2 and even neutralized the more closely bound SARS-CoV-1.
Promising Clinical Candidates
"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 McInerney's group.
The researchers are currently applying the same methods to identify nanoparticles from this group that are best able to neutralize Omicron, the now-dominant SARS-CoV-2 variant.
Once established, these libraries can be expanded and extracted for nanobodies that neutralize new emerging variants,” says Associate Professor Ben Morell, who is also co-lead author of both studies.
References:
1. Hankee L, Das H, Sheward DJ et al. The bispecific monomeric nanobody induces acute cyclic dimers and neutralizes SARS-CoV-2 in vivo. Nat Combs. 2022; 13 (1): 155. doi: 10.1038/s41467-021-27610-z.
2. Hanky Liu, Sheward Daniel J, Banku Alec et al. Multivariate mining of an alpaca immune repertoire identifies potent SARS-CoV-2 nanobodies. Science lecturer. 8 (12): eabm0220. doi: 10.1126/sciadv.abm0220.
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