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Mar 18, 2020
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Biologists from the Netherlands have discovered the first antibody to neutralize the new coronavirus. But the cure is still far

A group of researchers from the Netherlands published a preprint on biorxiv.org stating that it was found the first monoclonal antibody blocking SARS-CoV-2 and SARS-CoV coronaviruses. The discovery can be used to develop a drug against COVID - 10.

Biologists from the Erasmus Medical Center (structural unit Erasmus University in Rotterdam) and Utrecht University have developed antibodies to control the coronavirus that caused the COVID epidemic - 19. According to their claims, they found a monoclonal antibody that neutralizes both SARS-CoV-2 and SARS-CoV (SARS virus 2002 of the year). To do this, they used antibodies obtained in previous years to combat other types of coronaviruses, successively testing them for affinity for a new virus. Group article from specialists is still under consideration in the journal Nature and is available as a preprint on biorxiv.org .

According to lead author Frank Grosveld in an interview with the Erasmus University website erasmusmagazine.nl , fifteen years ago, he began research on the possibility of growing antibodies for humans in the body of laboratory mice. The results were encouraging, so that on the basis of the Medical Center of the University of Erasmus (Erasmus MC) and several other institutes, a research and production company ( Harbor Antibodies BV ) was created. In particular, she was involved in the production of antibodies for the treatment of tumors. During several outbreaks of coronavirus infections, she also developed antibodies for them.

Coronavirus S proteine attaching to cell receptor S the coronavirus protein attaches to the cell receptor. Image: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Antibodies that neutralize coronaviruses usually respond on their spike-like proteins (trimeric glycoproteins, or S-proteins, visible as characteristic processes of the “corona” in all images of the virus). With the help of S-proteins, viruses “attach” to the transmembrane receptors of the cell; in this case, the target is called ACE-2, or “angiotensin converting enzyme 2”, and the mechanism of “clinging” to it in the new coronavirus is identical to the mechanism that causes SARS (SARS epidemic 2002 of the year). The spike-like proteins of both viruses, SARS-CoV-2 and SARS-CoV, are also structurally similar and very close (51, 5% similarity) in amino acid sequences.

Based on the results of this research cycle, the laboratory still has at its disposal a collection of 47 of the species containing the corresponding antibody cell lines ("hybridomas") that responded to the previous version of the coronavirus dangerous to humans, that is, SARS-CoV. After the outbreak of a new epidemic, all of these samples were mothballed and examined for the possibility of responding to a new virus. Four of the antibodies according to the results of enzyme-linked immunosorbent assay (ELISA) reacted to a new type of virus, and one of them, with the designation 22 D 03, judging by the test results, it was able to suppress both clones, acting in the same way on the spike-like protein of the SARS-CoV and SARS-CoV-2 viruses. This discovery, reinforced by 10 pages of additional materials, and formed the basis of the article now being considered in Nature . According to general ethical principles, before passing the first round of reviewing, researchers and their educational institution cannot make a statement to the press, although, of course, it is not forbidden to talk about their developments in an interview format on the university page. Only after accepting the article for publication should we expect appropriate releases, which will be distributed much wider.

This is not about a vaccine, but about a medicine that can potentially stop the development of the disease. The vaccine usually contains a protein that is somehow connected with the virus (attenuated strain or inactivated virus), which, once in the body, leads to the emergence of "memory cells", or B-lymphocytes that generate the corresponding antibodies. On the contrary, the medicine itself supplies antibodies (in this case, an IgG1-type immunoglobulin) to neutralize the virus, and can maintain an acceptable level of protection for some time, for example, days or weeks, until recovery. According to F. Grossfeld, the development of a vaccine would take about two years, while a drug using open antibodies could appear earlier.

Immunoglobulin 20 D 03 (antibody; backlighting with DAPI fluorescent dye) binds in GFP -labeled cells (with green fluorescent protein) with spike protein of two coronaviruses. The third virus, MERS, which the antibody obviously does not act on, is used for negative control (placebo principle). From the article F. Grosveld et al .

What could be done in the end, when there will be a medicine, and what will be written in the news?

In the language of the protocol for clinical trials, the results of Dutch biologists are stage zero preclinical trials : studies are performed in vitro (“in vitro”) or in laboratory animals. There is not even a medicine / vaccine - the principle of action of a potential active substance in a future medicine is checked and it is determined whether to continue to mess with it at all. Further, the proposed drug (which is not yet available) undergoes clinical trials that are divided into several phases. Even the very first phase involves the participation of several dozen test subjects, and at this stage it is only determined whether this drug can be administered to a person at all (toxicity and tolerance): we are not talking about effectiveness. And here about %) are eliminated)% of candidates. Only in the second phase, in which there are several hundred subjects, can the question of the effectiveness of the new drug be raised. But the “real” trials, after which the next wonderful pills can get the status of a medicine and the chances of being included in the clinical protocols, are the third phase 85721, randomized controlled multicenter trials in which the number of subjects can be measured in thousands.

As follows from the article itself and from the interview of the lead author, there is no question about the medicine - only the antibodies themselves that were left after the research were proposed work with previous dangerous varieties of coronavirus. The minimum program is the use of these antibodies to develop antigen detection tests. Even if a pharmaceutical company can take this development into service and launch a drug on its basis, it will take several years to reach the level of the drug when this strain of the virus may be irrelevant.

And the most important thing: from a "prospective development", which even ends with the publication of the results in a level journal Nature or Science , about 1% of such drugs survive to a sane level of evidence-based medicine (A or B).

At the same initial stage there are several similar studies that were presented in the news as “developed vaccines / drugs for coronavirus”. On a special page there is a summary of information on drugs that are currently undergoing clinical trials of various stages. At the time of writing this note, two vaccines were declared there directly from SARS-CoV-2, from the companies Moderna, Inc. and Inovio Pharmaceuticals , both on zero (preclinical) stage, and several more drugs related to other types of coronaviruses that are dangerous for humans, that is, SARS-CoV and MERS-CoV. There is also news on the network about several more candidate vaccines outside this list, for example, this one from Chinese virologists. Most likely, all of them are far from clinical use.

In an interview with the Erasmus University website, a statement was made that immunoglobulin 20) 11 - almost the first antibody created, namely blocking 85720 new coronavirus. A quick search on antibodies-online.com yields at least ten drugs, designated as antibodies to SARS-CoV-2, with different principles of action (i.e. reacting to different proteins virus, including its "spike") and affordable pricing 250 Euro for 0.1 mg. All of them are labeled as “intended only for research purposes”, apparently, their purpose is to identify virus proteins in laboratory experiments, and certainly not a cure. Specialists can themselves evaluate the scientific novelty of the work done on available materials; In any case, we will receive more detailed information after accepting the article for publication and the reaction of the scientific community.

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