Llama antibodies have neutralized an intestinal infection virus
Noroviruses cause hundreds of millions of intestinal infections each year and claim many lives, especially among susceptible children. The authors of the study have proposed a new way to treat norovirus infections - with the help of special, very small lam antibodies (nanobodies). To prove their effectiveness, scientists used "mini guts" - a model of a human organ, which was grown in the laboratory.
If a person falls ill with an intestinal infection or gastroenteritis, the culprit is most often norovirus. Indeed, norovirus infections are the most widespread: every year they are sickened about 684 million people around the world, of which 212 thousand die from complications. Children, the elderly and those with chronic diseases are particularly affected.
Human noroviruses are very diverse: there are 10 groups, among which groups GI, GII, GIV, GVIII and GIX infect humans. The viruses of subgroup GII.4 are particularly widespread and insidious, as they can bypass immunity that has developed to other, earlier variants of this virus. This is roughly the case with influenza or the SARS-CoV-2 coronavirus that causes Covid-19. Thus, immunity to noroviruses is difficult to develop and unstable.
All this motivated the authors of a new paper in the journal Nature Communications to search for a new method of therapy for norovirus infection. They paid attention to nanobodies - antibodies (immunoglobulins) that are synthesized in the body of the Lama glama. This is a relative of the camel from South America, similar to it in many ways, including special immune system proteins.
The immunoglobulins of llamas and camels consist of just two polypeptide chains instead of the usual four. Having learned about this, scientists have created on their basis "nanobodies" (nanobodies) - a similar immunoglobulin with a single small section. The very one that serves for specific binding of the target - hypervariable. Nanobodies are ten times smaller in mass than human immunoglobulin, but they are not inferior to it in specificity of binding, and in reliability they may even surpass it.
Nanobodies have proven to be a promising method of treatment of viral diseases such as hepatitis B, influenza, HIV, polio and so on. This time it is the turn of intestinal viruses, the main cause of enterocolitis.
To begin with, biologists injected llamas with different strains of human norovirus and obtained nanobodies to them - they were designated as M4. Next, they created organoids of the human intestine, or "mini-guts". This is a model of a part of the human body, which consists of the same cells and well reproduces the behavior of real tissues.
Finally, "mini-guts" infected with norovirus of different strains and evaluated how the infection is affected by nanobodies M4. It turned out that they effectively prevent infection, and not only the most "popular" strain of GII.4, but also those lines of the virus from which it originated and which circulated in the population earlier.
Moreover, the mechanisms of norovirus inhibition by llama antibodies have become known. These small proteins literally wedge themselves into the gaps created on the surface of viral particles by shape-shifting and quickly destroy them.
The authors hope that their result will soon become the basis for effective therapy of unpleasant and dangerous intestinal infections.