Alpacas provide new hope for a COVID-19 cure

On several acres of rolling green pasture in Bairnsdale there’s a very special herd of alpacas.

A curious tourist driving past the East Gippsland site in Victoria would not notice anything unusual; just a bunch of oddly shaped creatures, chewing cud, spitting at each other and anything that comes too close.

But in their veins flow tiny fragments of the virus that causes COVID-19.

They are the start of a project that could one day turn their unique virus-busting antibodies into a powerful treatment for the global pandemic.

Australian researchers, working with the super-intense light generated by the Australian Synchrotron, are attempting to extract and purify them. If the research goes well, they could later be injected into or inhaled by patients – a potent preventative or cure.

Surprisingly, alpacas are objects of fascination for researchers who study the immune system.

Most animals, including humans, produce just a single type of antibody, a Y-shaped protein used for neutralising viruses.

Coronaviruses like SARS-CoV-2, which causes COVID-19, are covered in sharp spike-proteins that are used to enter human cells. The top part of the Y on an antibody sticks to that spike, gumming up the spike – like chewing gum on a shoe – so that it can’t stick to the cell.

Camelids, a species that includes alpacas, llamas and camels, produce two types of antibodies, one similar to human antibodies and the other dramatically smaller, called a nanobody.

Sharks make them too, but they are slightly harder to work with than alpacas.

“To be honest, no one really knows why camelids make them,” says Associate Professor Wai-Hong Tham, joint head of infectious diseases at the Walter and Eliza Hall Institute in Melbourne, where she is leading the research.

“But they are really special. They are really small, very stable, and extremely sticky to the spike protein.”

The nanobody’s small size allows it to tumble into pockets and crevices on the coronavirus’s spike protein, getting around any defences the virus may have set up and sticking onto parts of the spike a normal-sized antibody can never fit onto.

That makes it much more effective at gumming up the virus. Get those nanobodies out of llamas and into humans, and you could have a potent COVID-buster.

That will take some time. Scientists also need to find ways of making the nanobodies look like human cells, so our immune system does not attack them too. Therapies using cloned human antibodies are likely to be available much sooner.

But nanobody therapy is theoretically much more powerful, and is no pipe dream. Nanobodies are in final human trials around the world for several diseases, including HIV, and are already part of one approved drug for blood clots.

They are fiendishly difficult to work with, in part because they are unbelievably tiny: about 10 nanometres across – not much wider than the helix of your DNA, and about as long as your fingernails grow in 10 seconds.

Conventional microscopes cannot see things that small because the wavelength of visible light is too big.

That’s where the ANSTO synchrotron comes in. A huge ring of magnets the size of a football field, in Clayton in Melbourne’s south-east, accelerates electrons to almost the speed of light. As they bend around the ring, their movement generates extremely intense X-ray light.

This light can then be shone at the antibodies – held inside a crystal – to study their shape and how they bind to SARS-CoV-2’s spike.

“Then you can look at how other molecules react to the spike. If you can understand how the cells are a lock and the spike protein is a key, you can understand how to stop the virus entering our cells,” says Professor Michael James, senior principal research scientist at the synchrotron.

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