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Recently, there have been cases of secondary infection of coronary pneumonia in many countries around the world.
the development of new crown vaccines and drugs is in full swing, and many "candidates" have entered clinical trials, the results so far have not been obvious.
, the scientists took a different approach and took aim at the alpaca's antibodies.
September 4th scientists from the Karolinska Institute in Stockholm, Sweden, published their latest study, Nature Communications: Alpaca nanoantibodies can mediate SARS-CoV-2 by blocking the interaction of the subjects.
antibodies to alpacas are so good? As a candidate for specific therapies, alpaca-sourced monostructure domain antibody fragments (also known as VHH or nanoantibodies) have several advantages over conventional antibodies.
they are about one-tenth the size of conventional antibodies, they retain specificity and affinity similar to conventional antibodies and are easier to clone, express, and operate.
antibody can be expressed in large quantities in bacteria and shows high thermal stability and solubility, making it easy to mass produce and reduce costs.
addition, they can be low to increase affinity or prolong serum half-life, which is essential for their use as antiviral drugs in humans.
, they have proven to be highly effective inhibitors of viral infections in the body, particularly respiratory infections, and can be easily humanized through existing programmes.
the alpaca antibody be able to merkin SARS-CoV-2? The researchers first isolated a nanoantibod, Ty1, from immune alpacas that specificly binds to the BINDING domain of SARS-CoV-2 prickly proteins.
, they conducted in-body and introphy experiments using SARS-CoV-2 prickly protein prosthetic lysovirus particles.
results show that Ty1 mediums the SARS-CoV-2 fake virus in an IC 50 value of 0.77 μg / ml (54 nM).
when Ty1 is expressed in mammalian cells in the form of Fc fusion proteins, effective melioth antibodies may be further enhanced to? 12 ng / ml.
by specific to Ty1, the researchers found that Ty1, with its natural configuration, highly specifically identified viral pyrethrins in SARS-CoV-2-infected cells.
background in these experiments also suggests that Ty1 is a highly specific tool for research, diagnosis, and treatment.
How does Ty1 medium SARS-CoV-2 alpaca antibodies by binding to SARS-CoV-2 hedgehog proteins? To understand the meso-mechanism, the researchers assessed the effects of Ty1 on the binding domain of SARS-CoV-2 to the binding domain of SARS-CoV-2 (RBD) to the binding of the subject angiosin conversion enzyme 2 (ACE2).
test results show that Ty1 directly blocks the binding of RBD to its host cell subject ACE2.
the specificity and high affinity binding of Ty1 and RBD has also been demonstrated in dynamic biofilm layer interference (BLI) experiments: Ty1 binds to RBD with a high affinity of approximately 5-10 nM.
RBD combined K D and Ty1 of 5-10 nM to understand the structural basis for effectively mediated SARS-CoV-2, the researchers used cryoelectromes to structurally determine the pre-integration stable SARS-CoV-2 synth extraterritory that formed a complex with Ty1.
found that Ty1 was bound to the virus's RBD with "up" and "down" configurations, and that nanoantibodies remained in a similar binding direction to RBD regardless of whether the RBD configuration was "up" or "down".
Ty1 binds to RBD with "up" and "down" configurations and prevents ACE2 from joining because the host cell-receiving ACE2 can only bind to RBD with an "up" configuration, so the path of SARS-CoV-2 and ACE2 is spatially obstructed on both sides.
in short, the binding position of ACE2 to viral RBD is encroached upon by the Ty1 nanometer antibody of the "up" and "down" configurations.
, in the spike trimer, any two of the three RBD binding points available adequately impede the virus's binding to the host cell receptor.
conclusion, this study demonstrates that alpaca nanoantibodies play a role in mediate SARS-CoV-2 by blocking the interaction between the virus and host cells.
, Ty1 is expected to be on the list of antiviral drug candidates.
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