Researchers identify nanobody that may prevent COVID-19 infection

Date:
September 4, 2020
Source:
Karolinska Institutet
Summary:
Researchers have identified a small neutralizing antibody, a
so-called nanobody, that has the capacity to block SARS-CoV-2 from
entering human cells. The researchers believe this nanobody has
the potential to be developed as an antiviral treatment against
COVID-19.



FULL STORY ========================================================================== Researchers at Karolinska Institutet in Sweden have identified a small neutralizing antibody, a so-called nanobody, that has the capacity to
block SARS-CoV-2 from entering human cells. The researchers believe this nanobody has the potential to be developed as an antiviral treatment
against COVID-19. The results are published in the journal Nature Communications.


==========================================================================
"We hope our findings can contribute to the amelioration of the
COVID-19 pandemic by encouraging further examination of this nanobody
as a therapeutic candidate against this viral infection," says Gerald McInerney, corresponding author and associate professor of virology at
the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

The search for effective nanobodies -- which are fragments of antibodies
that occur naturally in camelids and can be adapted for humans -- began
in February when an alpaca was injected with the new coronavirus' spike protein, which is used to enter our cells. After 60 days, blood samples
from the alpaca showed a strong immune response against the spike protein.

Next, the researchers cloned, enriched and analysed nanobody sequences
from the alpaca's B cells, a type of white blood cell, to determine which nanobodies were best suited for further evaluation. They identified one,
Ty1 (named after the alpaca Tyson), that efficiently neutralizes the
virus by attaching itself to the part of the spike protein that binds
to the receptor ACE2, which is used by SARS-CoV-2 to infect cells. This
blocks the virus from slipping into the cells and thus prevents infection.

"Using cryo-electron microscopy, we were able to see how the nanobody
binds to the viral spike at an epitope which overlaps with the cellular receptor ACE2- binding site, providing a structural understanding for
the potent neutralisation activity," says Leo Hanke, postdoc in the
McInerney group and first author of the study.

Nanobodies offer several advantages over conventional antibodies as
candidates for specific therapies. They span less than one-tenth the
size of conventional antibodies and are typically easier to produce cost-effectively at scale.

Critically, they can be adapted for humans with current protocols and
have a proven record of inhibiting viral respiratory infections.

"Our results show that Ty1 can bind potently to the SARS-CoV-2 spike
protein and neutralize the virus, with no detectable off-target activity"
says Ben Murrell, assistant professor in the Department of Microbiology,
Tumor and Cell Biology and co-senior author of the publication. "We
are now embarking on preclinical animal studies to investigate the
neutralizing activity and therapeutic potential of Ty1 in vivo."
This project is the first arising from the CoroNAb consortium, which is coordinated by Karolinska Institutet, and funded by the European Union's Horizon 2020 research and innovation programme. Additional funding for
this project was obtained from the Swedish Research Council, and KI
Development Office.

The sequence of Ty1 is available in the scientific article and will also
be posted on the NCBI GenBank sequence data base under the accession
code MT784731.


========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Leo Hanke, Laura Vidakovics Perez, Daniel J. Sheward, Hrishikesh
Das, Tim
Schulte, Ainhoa Moliner-Morro, Martin Corcoran, Adnane Achour,
Gunilla B.

Karlsson Hedestam, B. Martin Ha"llberg, Ben Murrell, Gerald
M. McInerney.

An alpaca nanobody neutralizes SARS-CoV-2 by blocking
receptor interaction. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020- 18174-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200904090314.htm

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