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Scientists in Belgium have won a tiny victory over COVID-19, the new coronavirus infection that has affected over 3.7 million people globally. They have been able to isolate and use an antibody from a llama to neutralise SARS-CoV-2 in a lab.
SARS-CoV-2 causes COVID-19. A llama is a woolly mammal originally from South America. And the research was led by Professor Xavier Saelens at the VIB-UGent Center for Medical Biotechnology, in close collaboration with Jason McLellan's lab at the University of Texas at Austin, US.
The findings, to be published in the peer-reviewed journal Cell, could be significant at a time when vaccine scientists and medical researchers are working against the clock to find an effective therapy for COVID-19.
Read on to know why a llama was chosen for this research and what the findings mean.
What's special about llama antibodies?
Let's start at the beginning: When something foreign and potentially dangerous enters the body, our blood plasma responds by making antibodies to fight off this threat. Human antibodies are basically proteins. Also known as immunoglobulin or IG proteins, antibodies look like the letter “Y”. The top edges of the “Y” have specific sites for binding with the pathogen to neutralise it. There’s a specific antibody for each and every antigen we’ve been exposed to throughout our lives!
In addition to these "conventional" antibodies, llamas also make nanobodies that have a slightly different structure: nanobodies are made with heavy-chain-only proteins. They have shorter arms, which the nanobody can use to attach itself to the virus and block its entry into the lungs. (According to the researchers, there are other animals, like sharks, that also make nanobodies, but llamas are obviously easier to work with.)
How does the coronavirus enter the lungs in the first place?
A coronavirus is basically a single strand of RNA (genetic material) wrapped in a protective shell with spike proteins on it. These proteins, which give the virus its shape (corona or crown-like) and name, are of different types. One of these spike proteins, called the S-proteins, are crucial to how the virus gains entry into the lungs: these S-proteins fit perfectly (almost like a jigsaw puzzle) into receptors called the ACE2 receptors on our lungs. Once this happens, the virus can cross into the healthy cells and use its resources to make millions of copies of itself.
However, if something else goes and attaches itself to these same S-proteins first, they are no longer free to attach to the ACE2 receptors. When they can no longer attach to the ACE2 receptors, they can't gain entry into healthy cells!
For this reason, the S-proteins have also garnered the attention of scientists as a potential way to block the entry of this virus into healthy cells.
What exactly did the scientists in Belgium do?
Professor Xavier Saelens and the team had been working with coronaviruses since before this pandemic. They had injected a llama called Winter with S-proteins from the first SARS coronavirus and the MERS coronavirus. Now, previous research had already helped them identify one nanobody that was excellent at fusing with just the right S-proteins to block the entry of SARS1 into healthy cells. Recently, the scientists used the same nanobody to check if it could bind with S-proteins in the COVID-19, too. And it worked!
The first SARS caused an outbreak of severe acute respiratory syndrome in 2002-03.
The Belgian scientists appear to have also found a way to administer these nanobodies or smaller single-domain antibodies through a nebulizer or inhaler, to block the entry of the virus. As COVID-19 is a respiratory pathogen, inhaling the antibody gets it straight to the infection site.
So, would this result in some type of antibody therapy?
It's too early to say. That said, the scientists plan to do more research on this. They also hope that the antibodies can eventually be used for prophylaxis - or prevention - of the disease. However, early research has also shown that this treatment could provide protection for up to two months only.
In the past, llama antibodies have been used for important research on viruses like HIV. These nanobodies could also serve a similar purpose, to further the research on COVID-19.
Why is everybody so interested in antibody tests and therapy right now?
There are two reasons why antibodies are of particular interest right now. One is because they can help us determine who has had COVID-19 already. This is what rapid antibody tests do. The second reason is that people who have recovered from COVID-19 have antibodies that can help others recover, too. Taking these antibodies from recovered patients to transfuse into another patient is known as passive antibody therapy or convalescent plasma therapy.
The growing interest in antibody treatment during the COVID-19 pandemic is understandable: convalescent plasma therapy is one of the oldest ways to deal with an outbreak. This therapy was also used during the first Ebola virus outbreak in the Democratic Republic of the Congo in 1976.
What could this mean for the treatment of COVID-19?
The llama antibody is being touted as the first known antibody that is able to counter both the SARS-CoV-1 and the SARS-CoV-2 viruses, the former responsible for the 2002-03 outbreak. The team studying this antibody had originally begun research for the SARS and MERS-causing viruses. It is also one of the first antibodies developed that is able to neutralize the SARS-CoV-2 virus.
Several animals - their numbers going into millions - are used for the production or discovery of new types of antibodies which are able to fight off certain antigens that the human immune system is not able to fight naturally. However, the EU Directive on the protection of animals used for scientific purposes requires animals not be used for scientific research where there is a non-animal alternative available.
