Llama antibodies may well be effective against SARS-CoV-2 variants

Are camels at the core of a new treatment against Covid-19? It is certain that these animals have small antibodies in humans, which are absent, which, according to Australian scientists, neutralize SARS-CoV-2 and some of its variants.

To end Universal epidemic From COVID-19, Scientific ideas are not lacking. The most unexpected involves Lamas. Actually, the camel produces very little Antibodies, Nano-antibodies, are absent in humans. Several studies have highlighted the ability of nano-antibodies to neutralize SARS-CoV-2, but it has not yet been exploited to form a therapeutic or prophylactic treatment against Kovid-19. Really, experience In vivo Difficult with nano-antibodies because they filter quickly Rein After their injection. This does not prevent scientists from continuing their research efforts.

An Australian team has identified four nano-antibodies that prevent intermittent interactions. Protein S, also mutated, and ACE2 cellular receptor. Injected into mice before infection, nano-antibodies protect them from disease. They publish Their result in PNAS.

Coreloid nano-antibodies attack coronovirus

Nano-antibodies WNb2, 15, 7 and 36 were purified from the serum of two Australian camels, which are immunized by the S protein and its fraction, which interacts with ACE2, Receptor binding domain (RBD). Of the fifty different nano-antibodies generated after this vaccination, only four were already strongly bound to the S protein of SARS-CoV-2. They can be divided into two groups: WNb2 and 36 form cluster 1 and WNb7 and 15 form cluster 2.

They all attach themselves to RBD but not in the same place, they act non-competitively. So using them in cocktails will increase Their neutral power. Furthermore, N501Y mutations, located in RBD and present in many forms of anxiety, do not interfere with their binding.

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Tested as a preventive treatment in mice

Scientists also conducted experiments In vivo On mice. In their Make a contract, Nano-antibody Not used for medical purposes, but is prophylactic. That is, they are administered prior to infection to limit the development of covid-19. Nano-antibodies are injected inside Peritoneum Of Rodents, And 24 hours later they are infected with a human strain of SARS-CoV-2 with the N501Y mutation. After three days, scientists studied their state The lungs. Preventive treatment with one of the four nano-antibodies saved the lungs of almost all rodents. Only one, immunized with WNb2, exhibits tissue damage in the lungs. Rate also affected treatmentARN Viral, which was reduced by a factor of 10,000 in treated animals.

Preventive treatment with nano-antibodies, alone or in cocktails, may be considered in those who respond poorly VaccinationAccording to scientists. Nano-antibodies may also be interesting to control the spread of more infectious variants of coronaviruses.

A few months ago, the Winter Lama made it possible to identify nano-antibodies (V)HH), produced by very small, single-chain antibody camels, which Neutral SARS-CoV-2.

A publication in Science, Published on November 5, describes a similar story, except that researchers at the University of Pittsburgh chose another llama, Wally. They also used a different approach that made it possible to separate nano-antibodies, which have neutralizing power, According to him, Is 100 to 1,000 times more than that of Winter.

Small antibodies extracted from llam

Wally was vaccinated with part of Protein s That recognizes the cellular receptor, Receptor binding domain (RBD). After about two months, scientists extracted from it Son plasma famous Nano-antibody.

In the experiment on winter, nano-antibodies to the S protein of SARS-CoV-2 were the most affected. Phase performance. Here it is based on the technique of spectroscopy The mass Which allows the identification of several thousand high affinity nano-antibodies.

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Three nano-antibodies stand out: Nbs 89, 20 and 21. Therefore the neutralizing ability of this trio was tested during an experiment, determining the amount needed to neutralize 50% (IC50) of induced cellular damage. Possible. Virus in vitro. It turns out that very small amounts of these nano-antibodies are required to reach IC50 of the order of nanometers (0.045 nm for the most effective).

A special relationship with Receptor binding domain

Nbs 21 is the most commonly diagnosed nano-antibody of those identified Plasma By the valley. The strange way of connecting to RBD seems to be the reason. Thanks to the analysis of the crystallographic structure of the Nbs21 – RBD complex, it actually appears that this nano-antibody binds RBD solidly by multiple interactions. Anti water And polarons that completely cover RBD, when other nanoantibodies bind only to the outer loop of the protein.

They are more stable than nano-antibodies. Immunoglobulin Humans, they can be stored at room temperature for up to six weeks. Like other treatmentsResearchers at the University of Pittsburgh envisioned spreading their nano-antibodies through a spray to protect the respiratory tract from a possible infection.

Llama antibodies can beat coronovirus

Article published by Julie Kern on April 10, 2020

The plasma of a young Belgian llama contains specific small antibodies. The latter are able to neutralize infections of the coronarians, which are responsible not only for SARS, but also for Kovid-19.

Winter is a four-year-old lama who grazes peacefully in a meadow near the city of Ghent, Belgium. The young camel can also play an important role in research Treatment against Kovid-19.

Indeed, the winters were immunized with an infusion containing two coronavir surface proteins (protein S): a Mars-kow And this Saras-CoV-1. Scientists identified small neutralizing antibodies in llama plasma, which were shown to be effective against two pseudo-type virus particles Lentivirus Modified to express surface proteins of the coronavirus) mimics two coronovirus strains against which Winter has been vaccinated, as well as Saras-COV-2.

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Results of this study will appear in the journal Cell. An early version, but reviewed by peers already available.

Small neutralizing antibodies

These are a subclass of IgG specific specifically to camels called VHH. They have only one heavy chain whereas traditional IgG have one light chain and one heavy chain. Therefore VHH has only one variable domain, which is located on a heavy chain.

A crystallographic analysis made it possible to determine on which part of the virus the VHH reorganized from Winter’s plasma bind: the receptor binding domain (RBD) of the S protein. Their fair action Against Sars-CoV-1 and Mers-CoV in Cell Cultures in vitro. One of them, VHH-72, is able to neutralize the infection of the viral pseudo-particle mimic sarc-COV-1, but also that mimic sarc-COV-2.

Smaller than conventional IgG, VHH is stable and can be administered Via A spray inhale specifically for the treatment of respiratory infections. Scientists are hopeful that the neutralizing ability of Lama VHH makes them serious candidates for the treatment of Kovid-19.

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