Miniantibodies against coronavirus
A potential cure for COVID-19 based on miniantibodies
Sergey Syrov, XX2 century
Within the walls of the University of Pittsburgh School of Medicine, in search of a cure for COVID-19, a promising antibody component was identified that effectively blocks the reproduction of SARS-CoV-2, which is confirmed by animal experiments.
The work, the materials of which are published in the journal Cell (Li et al., High Potency of a Bivalent Human VH Domain in SARS-CoV-2 Animal Models), is interesting because the found molecule is noticeably smaller than other candidates for antibody-based antibody drugs and can be delivered to the body not only in the form of intravenous injections, but also subcutaneously or in the form of a spray.
The first experiments on the use of antibodies as a basis for the creation of a drug for the treatment of COVID-19 were reported relatively long ago. Unfortunately, this is not an easy and long-term case, and COVID-19 antibody therapy has not entered into everyday medical practice. To begin with, among the many antibodies produced by the body of a recovering person, it is necessary to find the most powerful and at the same time the safest. And it seems that the research team, which included employees of the University of Pittsburgh, their colleagues from the University of North Carolina at Chapel Hill (UNC), the University of Texas Medical Branch (UTMB) in Galveston and other scientific centers of the USA and Canada, it succeeded.
What is and what is interesting about the V H-Fc ab8 compound?
Let's try to figure it out. The V H-Fc compound is based on V H, a variable region of the heavy chain of immunoglobulin G (IgG1) with high affinity for the Fc receptor, ab8 is the same fragment that connects to the receptor–binding domain (RSD) of the spike protein of the virus, preventing it from contacting ACE2. According to published data, this connection is highly specific (there is nothing useful in the human body that V H-Fc ab8 could contact. The absence of a reaction with 5,300 different human membrane proteins has been confirmed) and is quite strong. It is noted that the known RSD SARS-COV-2 mutations did not occur in the region of the ab8 epitope, so that V H-Fc ab8 binds to all varieties of this coronavirus.
In order to test the effectiveness of V H-Fc ab8 as a cure for COVID-19, the researchers conducted animal studies. It turned out that even a small dose (2 mg / kg) of the drug reduces the intensity of virus reproduction tenfold on the second day of infection in a mouse model of the disease (it should be understood that the correct dosage for such a large animal as a human may be different). The introduction of V H-Fc ab8 reduced the secretion of mucus in the upper respiratory tract and reduced the level of inflammation in the lungs.
Size matters
V H-Fc ab8 can be called a miniantibody (molecular weight 80 kDa, twice lighter than the original immunoglobulin G1). Its pharmacokinetics are comparable to the pharmacokinetics of a full-sized antibody, but a noticeably smaller size can be useful, since such a compound penetrates both ordinary and tumor tissue much more easily. This means that V H-Fc ab8, if it becomes a cure for COVID-19, can be used even in the form of a spray.
A large stage of scientific work has been completed by publication in a prestigious journal, and in order to continue the development and its possible distribution, the biotechnology company Abound Bio has been created, which has received a patent for the antibody fragment ab8.
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