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Nanobodies inhibit SARS-CoV-2 infection
24 April 2021
Australian researchers have identified neutralising nanobodies that block the SARS-CoV-2 virus from entering cells in preclinical models.
The discovery paves the way for further investigations into nanobody-based treatments for COVID-19.
attaching to the virus ‘spike’ protein.
Image: Dr Drew Berry in collaboration with
Associate Professor Wai-Hong Tham
Published in PNAS, the research is part of a consortium-led effort, bringing together the expertise of Australian academic leaders in infectious diseases and antibody therapeutics at WEHI, the Doherty Institute and the Kirby Institute.
At a glance
- Researchers have identified nanobodies that effectively blocked the SARS-CoV-2 virus from entering cells in pre-clinical models of COVID-19 infection.
- Nanobodies – which are tiny immune proteins – could provide an alternative to conventional antibody treatments for COVID-19.
- By mapping nanobodies, the research team was able to identify a nanobody that recognised the SARS-CoV-2 virus, including emerging global variants of concern. The nanobody also recognised the original SARS-CoV virus (which causes SARS), indicating it may provide cross-protection against these two human coronaviruses.
Using alpaca ‘nanobodies’ to block COVID-19 infection
Antibodies are key infection-fighting proteins in our immune system. An important aspect of antibodies is that they bind tightly and specifically to another protein.
Antibody-based therapies, or ‘biologics’, harness this property of antibodies, enabling them to bind to a protein involved in disease.
Nanobodies are unique antibodies – tiny immune proteins – produced naturally by alpacas in response to infection.
As part of the research, a group of alpacas in regional Victoria were immunised with a synthetic, non-infectious part of the SARS-CoV-2 ‘spike’ protein to enable them to generate nanobodies against the SARS-CoV-2 virus.
Associate Professor Wai-Hong Tham, who led the research, said the establishment of a nanobody platform at WEHI allowed an agile response for the development of antibody-based therapies against COVID-19.
“The synthetic spike protein is not infectious and does not cause the alpacas to develop disease – but it allows the alpacas to develop nanobodies,” she said.
“We can then extract the gene sequences encoding the nanobodies and use this to produce millions of types of nanobodies in the laboratory, and then select the ones that best bind to the spike protein.”
Associate Professor Tham said the leading nanobodies that block virus entry were then combined into a ‘nanobody cocktail’.
“By combining the two leading nanobodies into this nanobody cocktail, we were able to test its effectiveness at blocking SARS-CoV-2 from entering cells and reducing viral loads in preclinical models,” she said.
Mapping nanobody binding
ANSTO’s Australian Synchrotron and the Monash Ramaciotti Centre for Cryo-Electron Microscopy were critical resources in the project, allowing the research team to map how the nanobodies bound to the spike protein and how this impacted the virus’ ability to bind to its human receptor.
Hariprasad Venugopal, Senior Microscopist from the Monash Ramaciotti Centre for Cryo-Electron Microscopy, said the study highlighted the importance of open-access to high-end Cryo-EM facilities.
“We were able to directly image and map the neutralising interaction of the nanobodies with the spike protein using Cryo-EM at near atomic resolution,” Mr Venugopal said.
“Cryo-EM has been an important drug discovery tool in the global response to the COVID-19 pandemic.”
By mapping the nanobodies, the research team was able to identify a nanobody that recognised the SARS-CoV-2 virus, including emerging global variants of concern. The nanobody was also effective against the original SARS virus (SARS-CoV), indicating it may provide cross-protection against these two globally significant human coronaviruses.
“In the wake of COVID-19, there is a lot of discussion about pandemic preparedness. Nanobodies that are able to bind to other human beta-coronaviruses – including SARS-CoV-2, SARS-CoV and MERS – could prove effective against future coronaviruses as well,” Associate Professor Tham said.
This work was made possible with funding from the Medical Research Future Fund, the Hengyi Group and the Victorian Government.
WEHI authors
Phillip Pymm, Amy Adair, Li-Jin Chan, James Cooney, Cody Allison, Matthew O’Neill, Li Lynn Tan, Melanie H. Dietrich, Damien Drew, Marcel Doerflinger, Michael Dengler, Marc Pellegrini, Alisa Glukhova and Wai-Hong Tham.
Media inquiries
M: +61 475 751 811
E: communityrelations@wehi.edu.au
Super Content:
The Australian Government will invest $3M in Walter and Eliza Hall Institute research programs that are developing new classes of medicines for COVID-19.
WEHI researchers are studying ‘nanobodies’ – tiny immune proteins made by alpacas – in a bid to understand whether they might be effective in blocking SARS-CoV-2, the virus that causes COVID-19.
WEHI researchers are using extremely small antibodies that occur naturally in alpacas – called nanobodies – to develop biologics that could prevent the COVID-19 coronavirus from binding to human cells – the first step in the virus infection cycle.
Our researchers are working towards better approaches to diagnose, treat and prevent the spread of coronaviruses, both to address the current COVID-19 global outbreak as well as in preparedness for likely future coronaviral disease outbreaks.
Medical researchers use antibodies to help answer fundamental biological questions, for example understanding how specific proteins behave, and to assist in developing new therapies.
Find out about antibody-based research at WEHI.
The COVID PROFILE study will use blood samples from people who have recovered from COVID-19, and their close contacts, to look in detail at how immunity to the disease develops, how long it lasts and what happens when immunity is lost.
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