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Alpaca nanobodies potently neutralize SARS-CoV-2 variants

Date:
March 25, 2022
Source:
Karolinska Institutet
Summary:
Researchers have developed a novel strategy for identifying potent miniature antibodies, so-called nanobodies, against emerging SARS-CoV-2 variants. The approach led to the discovery of multiple nanobodies that in cell cultures and mice effectively blocked infection with different SARS-CoV-2 variants. The findings could pave the way for new treatments against COVID-19.
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FULL STORY

Researchers at Karolinska Institutet in Sweden have developed a novel strategy for identifying potent miniature antibodies, so-called nanobodies, against emerging SARS-CoV-2 variants. The approach led to the discovery of multiple nanobodies that in cell cultures and mice effectively blocked infection with different SARS-CoV-2 variants. The findings, which are described in the journalsNature CommunicationsandScience Advances, could pave the way for new treatments against 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 at the Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, and joint senior author of both studies.

Despite the roll-out of vaccines and antivirals, the need for effective therapeutics against severe COVID-19 infection remains high. Nanobodies -- which are fragments of antibodies that occur naturally in camelids and can be adapted for humans -- are promising therapeutic candidates as they offer several advantages over conventional antibodies. For example, they have favourable biochemical properties and are easy to produce cost-effectively at 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 immunised with SARS-CoV-2 antigens.

The first report inNature Communicationsdescribes a single nanobody, Fu2 (named after the alpaca Funny), that significantly reduced the viral load of SARS-CoV-2 in cell cultures and mice. Using electron cryo-microscopy, the researchers found that Fu2 naturally binds to two separate sites on the viral spike, thus inhibiting the virus' ability to enter the host cell. 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.

The researchers next delved deeper into the alpaca's nanobody repertoire by combining a range of advanced laboratory techniques and computational methods, resulting in a library of nanobodies described in detail.

The results, presented inScience Advances, revealed additional nanobodies that in cell cultures and mice effectively cross-neutralized both the founder and beta variant of SARS-CoV-2 and even neutralized the more distantly related SARS-CoV-1.

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"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.

The researchers are currently applying the same techniques to identify which nanobodies from this set are best able to neutralize Omicron, the now dominating SARS-CoV-2 variant.

"Once established, these libraries can be expanded and mined for nanobodies that neutralize new emerging variants," says Assistant Professor Ben Murrell, also joint senior author of both studies.

Funding was provided by David and Astrid Hagelén Foundation, the Clas Groschinskys Minnesfond and a Jonas Söderquist's scholarship, European Union's Horizon 2020 research and innovation program, Swedish Research Council, and Knut and Alice Wallenberg Foundation.

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Materialsprovided byKarolinska Institutet.注意:内容可能被编辑风格d length.


Journal References:

  1. 利奥汉克,Hrishikesh Das,丹尼尔·j·Sheward Laura Perez Vidakovics, Egon Urgard, Ainhoa Moliner-Morro, Changil Kim, Vivien Karl, Alec Pankow, Natalie L. Smith, Bartlomiej Porebski, Oscar Fernandez-Capetillo, Erdinc Sezgin, Gabriel K. Pedersen, Jonathan M. Coquet, B. Martin Hällberg, Ben Murrell, Gerald M. McInerney.A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo.Nature Communications, 2022; 13 (1) DOI:10.1038/s41467-021-27610-z
  2. Leo Hanke, Daniel J. Sheward, Alec Pankow, Laura Perez Vidakovics, Vivien Karl, Changil Kim, Egon Urgard, Natalie L. Smith, Juan Astorga-Wells, Simon Ekström, Jonathan M. Coquet, Gerald M. McInerney, Ben Murrell.Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralizing SARS-CoV-2 nanobodies.Science Advances, 2022; 8 (12) DOI:10.1126/sciadv.abm0220

Cite This Page:

Karolinska Institutet. "Alpaca nanobodies potently neutralize SARS-CoV-2 variants." ScienceDaily. ScienceDaily, 25 March 2022. /releases/2022/03/220325185907.htm>.
Karolinska Institutet. (2022, March 25). Alpaca nanobodies potently neutralize SARS-CoV-2 variants.ScienceDaily. Retrieved September 6, 2023 from www.koonmotors.com/releases/2022/03/220325185907.htm
Karolinska Institutet. "Alpaca nanobodies potently neutralize SARS-CoV-2 variants." ScienceDaily. www.koonmotors.com/releases/2022/03/220325185907. htm(2023年9月6日访问)。

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